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{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{Infobox_gene}}
{{Infobox_gene}}
'''Phospholipase C, gamma 1''', also known as '''PLCG1''', is a [[protein]] that in humans is encoded by the ''PLCG1'' [[gene]].<ref name="pmid3254788">{{cite journal | vauthors = Bristol A, Hall SM, Kriz RW, Stahl ML, Fan YS, Byers MG, Eddy RL, Shows TB, Knopf JL | title = Phospholipase C-148: chromosomal location and deletion mapping of functional domains | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 53 | issue = 2 | pages = 915–20 | year = 1988 | pmid = 3254788 | doi = 10.1101/sqb.1988.053.01.105 }}</ref><ref name="pmid2167438">{{cite journal | vauthors = Burgess WH, Dionne CA, Kaplow J, Mudd R, Friesel R, Zilberstein A, Schlessinger J, Jaye M | title = Characterization and cDNA cloning of phospholipase C-gamma, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase | journal = Molecular and Cellular Biology | volume = 10 | issue = 9 | pages = 4770–7 | date = September 1990 | pmid = 2167438 | pmc = 361079 | doi = 10.1128/mcb.10.9.4770}}</ref>
'''Phospholipase C, gamma 1''', also known as '''PLCG1''' and '''PLCgamma1''', is a [[protein]] that in humans involved in cell [[Cell growth|growth]], [[Cell migration|migration]], [[apoptosis]], and [[Cell proliferation|proliferation]]. It is encoded by the ''PLCG1'' [[gene]]<ref name="pmid3254788">{{cite journal | vauthors = Bristol A, Hall SM, Kriz RW, Stahl ML, Fan YS, Byers MG, Eddy RL, Shows TB, Knopf JL | title = Phospholipase C-148: chromosomal location and deletion mapping of functional domains | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 53 | issue = 2 | pages = 915–20 | year = 1988 | pmid = 3254788 | doi = 10.1101/sqb.1988.053.01.105 }}</ref><ref name="pmid2167438">{{cite journal | vauthors = Burgess WH, Dionne CA, Kaplow J, Mudd R, Friesel R, Zilberstein A, Schlessinger J, Jaye M | title = Characterization and cDNA cloning of phospholipase C-gamma, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase | journal = Molecular and Cellular Biology | volume = 10 | issue = 9 | pages = 4770–7 | date = September 1990 | pmid = 2167438 | pmc = 361079 | doi = 10.1128/mcb.10.9.4770}}</ref> and is part of the [[Phospholipase C|PLC]] superfamily.


== Function ==
== Function ==
PLCγ1 is a cell growth factor<ref name=":3">{{cite journal | vauthors = Koss H, Bunney TD, Behjati S, Katan M | title = Dysfunction of phospholipase Cγ in immune disorders and cancer | journal = Trends in Biochemical Sciences | volume = 39 | issue = 12 | pages = 603–11 | date = December 2014 | pmid = 25456276 | doi = 10.1016/j.tibs.2014.09.004 | url = http://discovery.ucl.ac.uk/1455633/1/TIBS_Katan_M.pdf }}</ref><ref name=":4">{{cite journal | vauthors = Lattanzio R, Piantelli M, Falasca M | title = Role of phospholipase C in cell invasion and metastasis | journal = Advances in Biological Regulation | volume = 53 | issue = 3 | pages = 309–18 | date = September 2013 | pmid = 23925006 | doi = 10.1016/j.jbior.2013.07.006 }}</ref> from the [[Phospholipase C|PLC]] superfamily. PLCγ1 is used during cell growth<ref name=":3" /> and in cell migration<ref name=":1">{{cite journal | vauthors = Jang HJ, Suh PG, Lee YJ, Shin KJ, Cocco L, Chae YC | title = PLCγ1: Potential arbitrator of cancer progression | journal = Advances in Biological Regulation | volume = 67 | pages = 179–189 | date = January 2018 | pmid = 29174396 | doi = 10.1016/j.jbior.2017.11.003 }}</ref> and apoptosis,<ref name=":4" /> all of which are vital cell processes that, if disrupted by mutations, can cause [[Cancer cell|cancerous cells]] to form within the body. Mutations in this protein show an increase in issues in cells regarding regulation of proliferation and their cell signaling.<ref name=":3" /> PLCγ1 roles are also involved in neuronal actin growth, calcium signaling, and brain development.<ref name=":2">{{cite journal | vauthors = Kang DS, Kim IS, Baik JH, Kim D, Cocco L, Suh PG | title = The function of PLCγ1 in developing mouse mDA system | journal = Advances in Biological Regulation | volume = 75 | pages = 100654 | date = January 2020 | pmid = 31558431 | doi = 10.1016/j.jbior.2019.100654 | s2cid = 203568510 }}</ref><ref name=":4" /><ref name=":1" /> It is highly regulated by multiple factors, such as [[Phosphoinositide 3-kinase|PIK3]], [[AMP-activated protein kinase|AMPK]], and [[PTK2|FAK]].<ref name=":4" /><ref name=":0">{{cite journal | vauthors = Lu X, Fu H, Chen R, Wang Y, Zhan Y, Song G, Hu T, Xia C, Tian X, Zhang B | display-authors = 6 | title = in vitro | journal = International Journal of Biological Sciences | volume = 16 | issue = 8 | pages = 1427–1440 | date = 2020 | pmid = 32210730 | pmc = 7085223 | doi = 10.7150/ijbs.42962 | url = http://www.ijbs.com/v16p1427.htm }}</ref> It is part of the [[Phosphatidylinositol (3,4,5)-trisphosphate|PIP3]] pathway and leads to and increase in calcium in the cells. In [[Neuron|neuronal cells]], PLCγ1 is highly involved in actin [[cytoskeleton]] organization and [[synaptic plasticity]].<ref name=":2" /> The basic PLCγ1 pathway, as scientists currently understand it, is seen below.
⚫
The protein encoded by this gene catalyzes the formation of [[inositol triphosphate|inositol 1,4,5-trisphosphate]] and [[diglyceride|diacylglycerol]] from [[phosphatidylinositol 4,5-bisphosphate]]. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of receptor-mediated [[tyrosine kinase]] activators. For example, when activated by [[Src (gene)|SRC]], the encoded protein causes the [[Ras (protein)|Ras]] [[guanine nucleotide exchange factor]] [[RASGRP1]] to translocate to the [[Golgi apparatus]], where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. The receptor protein tyrosine phosphatase PTPmu ([[PTPRM]]) is capable of dephosphorylating PLCG1.<ref name="pmid20506511">{{cite journal | vauthors = Phillips-Mason PJ, Kaur H, Burden-Gulley SM, Craig SE, Brady-Kalnay SM | title = Identification of phospholipase C gamma1 as a protein tyrosine phosphatase mu substrate that regulates cell migration | journal = Journal of Cellular Biochemistry | volume = 112 | issue = 1 | pages = 39–48 | date = January 2011 | pmid = 20506511 | pmc = 3031780 | doi = 10.1002/jcb.22710 }}</ref> Two transcript variants encoding different isoforms have been found for this gene.<ref>{{Cite web| title = Entrez Gene: PLCG1 phospholipase C, gamma 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5335| accessdate = }}</ref>
[[File:PLCG1_Pathway.jpg|center|thumb|506x506px|PLCG1 Pathway]]
⚫
The protein encoded by this gene catalyzes the formation of [[inositol triphosphate|inositol 1,4,5-trisphosphate]] (IP3) and [[diglyceride|diacylglycerol]] (DAG) from [[phosphatidylinositol 4,5-bisphosphate]]. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of receptor-mediated [[tyrosine kinase]] activators. For example, when activated by [[Src (gene)|SRC]], the encoded protein causes the [[Ras (protein)|Ras]] [[guanine nucleotide exchange factor]] [[RASGRP1]] to translocate to the [[Golgi apparatus]], where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. The receptor protein tyrosine phosphatase PTPmu ([[PTPRM]]) is capable of dephosphorylating PLCG1.<ref name="pmid20506511">{{cite journal | vauthors = Phillips-Mason PJ, Kaur H, Burden-Gulley SM, Craig SE, Brady-Kalnay SM | title = Identification of phospholipase C gamma1 as a protein tyrosine phosphatase mu substrate that regulates cell migration | journal = Journal of Cellular Biochemistry | volume = 112 | issue = 1 | pages = 39–48 | date = January 2011 | pmid = 20506511 | pmc = 3031780 | doi = 10.1002/jcb.22710 }}</ref> Two transcript variants encoding different isoforms have been found for this gene.<ref>{{Cite web| title = Entrez Gene: PLCG1 phospholipase C, gamma 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5335}}</ref>


Common to all PLC isozymes, PLCG1 consists of an N-terminal PH domain, which translocates PLC to the plasma membrane and binds PIP3;<ref>{{cite journal | vauthors = Singh SM, Murray D | title = Molecular modeling of the membrane targeting of phospholipase C pleckstrin homology domains | journal = Protein Science | volume = 12 | issue = 9 | pages = 1934–53 | date = September 2003 | pmid = 12930993 | pmc = 2323991 | doi = 10.1110/ps.0358803 }}</ref> four EF hands; an X and Y catalytic region comprising the TIM barrel; and a C-terminal C2 domain.<ref name="Gresset_2012">{{cite book | vauthors = Gresset A, Sondek J, Harden TK | title = Phosphoinositides I: Enzymes of Synthesis and Degradation | chapter = The phospholipase C isozymes and their regulation | volume = 58 | pages = 61–94 | date = March 2012 | pmid = 22403074 | pmc = 3638883 | doi = 10.1007/978-94-007-3012-0_3 | series = Subcellular Biochemistry | isbn = 978-94-007-3011-3 }}</ref> Specific to the PLCG isozymes is a large separation between the X and Y domains consisting of a split PH domain, tandem SH2 domains, and an SH3 domain.<ref name="Gresset_2012" /> The SH2 domains bind phosphorylated tyrosine residues on target proteins via their FLVR sequence motifs, activating the catalytic function of PLCg; and the SH3 domain binds to proline-rich sequences on the target protein.<ref name="Gresset_2012" />
Common to all PLC isozymes, PLCG1 consists of an N-terminal PH domain, which translocates PLC to the plasma membrane and binds PIP3;<ref>{{cite journal | vauthors = Singh SM, Murray D | title = Molecular modeling of the membrane targeting of phospholipase C pleckstrin homology domains | journal = Protein Science | volume = 12 | issue = 9 | pages = 1934–53 | date = September 2003 | pmid = 12930993 | pmc = 2323991 | doi = 10.1110/ps.0358803 }}</ref> four EF hands; an X and Y catalytic region comprising the TIM barrel; and a C-terminal C2 domain.<ref name="Gresset_2012">{{cite book | vauthors = Gresset A, Sondek J, Harden TK | title = Phosphoinositides I: Enzymes of Synthesis and Degradation | chapter = The phospholipase C isozymes and their regulation | volume = 58 | pages = 61–94 | date = March 2012 | pmid = 22403074 | pmc = 3638883 | doi = 10.1007/978-94-007-3012-0_3 | series = Subcellular Biochemistry | isbn = 978-94-007-3011-3 }}</ref> Specific to the PLCG isozymes is a large separation between the X and Y domains consisting of a split PH domain, tandem SH2 domains, and an SH3 domain.<ref name="Gresset_2012" /> The SH2 domains bind phosphorylated tyrosine residues on target proteins via their FLVR sequence motifs, activating the catalytic function of PLCg; and the SH3 domain binds to proline-rich sequences on the target protein.<ref name="Gresset_2012" />
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PLCG1 can be activated by [[receptor tyrosine kinase]]s (RTKs) and [[non-receptor tyrosine kinase]]s. For example, when activated, fibroblast growth factor receptor 1 and epidermal growth factor receptor are RTKs that have phosphorylated tyrosines, which provide docking sites for PLCG1 [[SH2 domain]]s.<ref name="Gresset_2012" /> The activated RTKs phosphoylate PLCG1 at tyrosines located at position 472, 771, 775, 783, and 1254.<ref>{{cite journal | vauthors = Bae JH, Lew ED, Yuzawa S, Tomé F, Lax I, Schlessinger J | title = The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site | journal = Cell | volume = 138 | issue = 3 | pages = 514–24 | date = August 2009 | pmid = 19665973 | pmc = 4764080 | doi = 10.1016/j.cell.2009.05.028 }}</ref> Non-receptor tyrosine kinases interact with PLCG1 in large complexes at the plasma membrane. For example, in T cells, Lck and Fyn ([[Src family kinase]]s) phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) on the T-cell antigen receptor (TCR).<ref name="Gresset_2012" /> The phosphorylated ITAMs recruit ZAP-70, which phosphorylates tyrosines in LAT and SLP-76. PLCg1 binds to LAT through its n-terminal SH2 domain and to SLP-76 via its [[SH3 domain]].<ref name="Gresset_2012" />
PLCG1 can be activated by [[receptor tyrosine kinase]]s (RTKs) and [[non-receptor tyrosine kinase]]s. For example, when activated, fibroblast growth factor receptor 1 and epidermal growth factor receptor are RTKs that have phosphorylated tyrosines, which provide docking sites for PLCG1 [[SH2 domain]]s.<ref name="Gresset_2012" /> The activated RTKs phosphoylate PLCG1 at tyrosines located at position 472, 771, 775, 783, and 1254.<ref>{{cite journal | vauthors = Bae JH, Lew ED, Yuzawa S, Tomé F, Lax I, Schlessinger J | title = The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site | journal = Cell | volume = 138 | issue = 3 | pages = 514–24 | date = August 2009 | pmid = 19665973 | pmc = 4764080 | doi = 10.1016/j.cell.2009.05.028 }}</ref> Non-receptor tyrosine kinases interact with PLCG1 in large complexes at the plasma membrane. For example, in T cells, Lck and Fyn ([[Src family kinase]]s) phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) on the T-cell antigen receptor (TCR).<ref name="Gresset_2012" /> The phosphorylated ITAMs recruit ZAP-70, which phosphorylates tyrosines in LAT and SLP-76. PLCg1 binds to LAT through its n-terminal SH2 domain and to SLP-76 via its [[SH3 domain]].<ref name="Gresset_2012" />


Has been shown to interact with [[CISH]] which negatively regulates it by targeting it for degradation.<ref name="Palmer_2015">{{cite journal | vauthors = Palmer DC, Guittard GC, Franco Z, Crompton JG, Eil RL, Patel SJ, Ji Y, Van Panhuys N, Klebanoff CA, Sukumar M, Clever D, Chichura A, Roychoudhuri R, Varma R, Wang E, Gattinoni L, Marincola FM, Balagopalan L, Samelson LE, Restifo NP | title = Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance | journal = The Journal of Experimental Medicine | volume = 212 | issue = 12 | pages = 2095–113 | date = November 2015 | pmid = 26527801 | pmc = 4647263 | doi = 10.1084/jem.20150304 }}</ref> The deletion of Cish in effector T cells has been shown to augment TCR signaling and subsequent effector cytokine release, proliferation and survival. The adoptive transfer of tumor-specific effector T cells knocked out or knocked down for CISH resulted in a significant increase in functional avidity and long-term tumor immunity. There are no changes in activity or phosphorylation of Cish's purported target, [[STAT5]] in either the presence or absence of Cish.
Has been shown to interact with [[CISH (gene)|CISH]] which negatively regulates it by targeting it for degradation.<ref name="Palmer_2015">{{cite journal | vauthors = Palmer DC, Guittard GC, Franco Z, Crompton JG, Eil RL, Patel SJ, Ji Y, Van Panhuys N, Klebanoff CA, Sukumar M, Clever D, Chichura A, Roychoudhuri R, Varma R, Wang E, Gattinoni L, Marincola FM, Balagopalan L, Samelson LE, Restifo NP | title = Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance | journal = The Journal of Experimental Medicine | volume = 212 | issue = 12 | pages = 2095–113 | date = November 2015 | pmid = 26527801 | pmc = 4647263 | doi = 10.1084/jem.20150304 }}</ref> The deletion of Cish in effector T cells has been shown to augment TCR signaling and subsequent effector cytokine release, proliferation and survival. The adoptive transfer of tumor-specific effector T cells knocked out or knocked down for CISH resulted in a significant increase in functional avidity and long-term tumor immunity. There are no changes in activity or phosphorylation of Cish's purported target, [[STAT5]] in either the presence or absence of Cish.


''[[In vitro]]'' studies have shown signs of PLCγ1 having many cell-motility functions, however ''[[in vivo]]'' have not been able to show a physiological role for PLCγ1.<ref name=":22">{{cite journal | vauthors = Kang DS, Kim IS, Baik JH, Kim D, Cocco L, Suh PG | title = The function of PLCγ1 in developing mouse mDA system | journal = Advances in Biological Regulation | volume = 75 | pages = 100654 | date = January 2020 | pmid = 31558431 | doi = 10.1016/j.jbior.2019.100654 | s2cid = 203568510 }}</ref> While PLCγ1 is well documented and easily found in the body, clear connections and roles for PLCγ1 have been difficult to find in ''in vivo'' studies. Despite this, there is still able to find links between levels of PLCγ1 and cancer patient survivability.
== Clinical significance ==

Researchers studying PLCg1 and its role in breast cancer metastasis discovered this gene can promote cancer metastasis and subsequently blocking it stopped cancer from spreading. Research is ongoing but this gene could lead to the development of new anti-cancer drugs.<ref name="urlScientists may be able to stop cancer spreading round the body - Telegraph">{{Cite web| url = https://www.telegraph.co.uk/health/healthnews/3758314/Scientists-may-be-able-to-stop-cancer-spreading-round-the-body.html | title = Scientists may be able to stop cancer spreading round the body | author = Smith R | authorlink = | date = 2008-12-14 | work = Health News | publisher = Telegraph.co.uk | pages = | archiveurl = | archivedate = | quote = | accessdate = 2008-12-17}}</ref><ref name="pmid19074886">{{cite journal | vauthors = Sala G, Dituri F, Raimondi C, Previdi S, Maffucci T, Mazzoletti M, Rossi C, Iezzi M, Lattanzio R, Piantelli M, Iacobelli S, Broggini M, Falasca M | title = Phospholipase Cgamma1 is required for metastasis development and progression | journal = Cancer Research | volume = 68 | issue = 24 | pages = 10187–96 | date = December 2008 | pmid = 19074886 | doi = 10.1158/0008-5472.CAN-08-1181 | doi-access = free }}</ref>
== Cancer ==
Mutations in PLCγ1 can lead to cancer cell proliferations and inhibition can lead to tumor growth.<ref name=":02">{{cite journal | vauthors = Lu X, Fu H, Chen R, Wang Y, Zhan Y, Song G, Hu T, Xia C, Tian X, Zhang B | display-authors = 6 | title = in vitro | journal = International Journal of Biological Sciences | volume = 16 | issue = 8 | pages = 1427–1440 | date = 2020 | pmid = 32210730 | pmc = 7085223 | doi = 10.7150/ijbs.42962 | url = http://www.ijbs.com/v16p1427.htm }}</ref> PLCγ1 is involved in cell proliferation, and mutations cause it to be over expressed and help the progression of tumor cells. This aspect of PLCγ1 also helps cancer migration and [[metastasis]] away from the original tumor cells.<ref name=":12">{{cite journal | vauthors = Jang HJ, Suh PG, Lee YJ, Shin KJ, Cocco L, Chae YC | title = PLCγ1: Potential arbitrator of cancer progression | journal = Advances in Biological Regulation | volume = 67 | pages = 179–189 | date = January 2018 | pmid = 29174396 | doi = 10.1016/j.jbior.2017.11.003 }}</ref><ref name=":42">{{cite journal | vauthors = Lattanzio R, Piantelli M, Falasca M | title = Role of phospholipase C in cell invasion and metastasis | journal = Advances in Biological Regulation | volume = 53 | issue = 3 | pages = 309–18 | date = September 2013 | pmid = 23925006 | doi = 10.1016/j.jbior.2013.07.006 }}</ref> There is also a link between PLCγ1 and [[Pyruvate dehydrogenase kinase|PDK]], the PDK-PLCγ1 pathway, which is a vital part of [[Invasion (cancer)|cancer cell invasion]].<ref name=":42" />

The inhibition of PLCγ1 is linked to a decrease in tumor growth and metastasis.<ref name=":02" /><ref name=":12" /> PLCγ1 is acting as a vital part in stopping apoptosis in cells, and thus by inhibiting PLCγ1 the body better allows programmed cell death and avoidance of tumors.<ref name=":02" /><ref name=":12" /> The main role found for PLCγ1 is cell growth, and this role in specific is why it is becoming more commonly studied for anti-cancer drugs.<ref name=":12" /><ref name=":42" /> Tissue samples from cancer patients the PLCγ1 levels are not elevated, however, regulatory factors for this proteins are lowered and that amplification of PLCγ1 is extremely high.<ref name=":12" /> The regulatory proteins that stop PLCγ1 have been turned off by the cell, which means that while there is no increase in the physical protein PLCγ1 there is an increase in how much work it is doing - nothing is stopping it from over working itself. Studies also showed that adding new regulatory to cells ''in vitro'' helped reduce previously amplified PLCγ1.<ref name=":02" /> This information has encouraged PLCγ1 becoming an anti-cancer drug target despite the issues that come with targeting intermembrane proteins.<ref name=":02" /><ref name=":42" /><ref name=":32">{{cite journal | vauthors = Koss H, Bunney TD, Behjati S, Katan M | title = Dysfunction of phospholipase Cγ in immune disorders and cancer | journal = Trends in Biochemical Sciences | volume = 39 | issue = 12 | pages = 603–11 | date = December 2014 | pmid = 25456276 | doi = 10.1016/j.tibs.2014.09.004 | url = http://discovery.ucl.ac.uk/1455633/1/TIBS_Katan_M.pdf }}</ref>


== Interactions ==
== Interactions ==
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{{div col|colwidth=20em}}
* [[BAG3]],<ref name = pmid10980614>{{cite journal | vauthors = Doong H, Price J, Kim YS, Gasbarre C, Probst J, Liotta LA, Blanchette J, Rizzo K, Kohn E | title = CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70 | journal = Oncogene | volume = 19 | issue = 38 | pages = 4385–95 | date = September 2000 | pmid = 10980614 | doi = 10.1038/sj.onc.1203797 | doi-access = free }}</ref>
* [[BAG3]],<ref name = pmid10980614>{{cite journal | vauthors = Doong H, Price J, Kim YS, Gasbarre C, Probst J, Liotta LA, Blanchette J, Rizzo K, Kohn E | title = CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70 | journal = Oncogene | volume = 19 | issue = 38 | pages = 4385–95 | date = September 2000 | pmid = 10980614 | doi = 10.1038/sj.onc.1203797 | doi-access = free }}</ref>
* [[CD117]],<ref name = pmid11071635>{{cite journal | vauthors = van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M | title = Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells | journal = Blood | volume = 96 | issue = 10 | pages = 3406–13 | date = November 2000 | pmid = 11071635 | doi = 10.1182/blood.V96.10.3406}}</ref><ref name = pmid7536744>{{cite journal | vauthors = Jhun BH, Rivnay B, Price D, Avraham H | title = The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit | journal = The Journal of Biological Chemistry | volume = 270 | issue = 16 | pages = 9661–6 | date = April 1995 | pmid = 7536744 | doi = 10.1074/jbc.270.16.9661 | doi-access = free }}</ref>
* [[CD117]],<ref name = pmid11071635>{{cite journal | vauthors = van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M | title = Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells | journal = Blood | volume = 96 | issue = 10 | pages = 3406–13 | date = November 2000 | pmid = 11071635 | doi = 10.1182/blood.V96.10.3406| url = https://pure.eur.nl/en/publications/395fb5fc-60e3-45d7-a9b1-fc7b9cc6b4bc | hdl = 1765/9530 | hdl-access = free }}</ref><ref name = pmid7536744>{{cite journal | vauthors = Jhun BH, Rivnay B, Price D, Avraham H | title = The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit | journal = The Journal of Biological Chemistry | volume = 270 | issue = 16 | pages = 9661–6 | date = April 1995 | pmid = 7536744 | doi = 10.1074/jbc.270.16.9661 | doi-access = free }}</ref>
* [[CD31]],<ref name = pmid10350061>{{cite journal | vauthors = Pumphrey NJ, Taylor V, Freeman S, Douglas MR, Bradfield PF, Young SP, Lord JM, Wakelam MJ, Bird IN, Salmon M, Buckley CD | title = Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31 | journal = FEBS Letters | volume = 450 | issue = 1–2 | pages = 77–83 | date = April 1999 | pmid = 10350061 | doi = 10.1016/s0014-5793(99)00446-9 | s2cid = 31471121 }}</ref>
* [[CD31]],<ref name = pmid10350061>{{cite journal | vauthors = Pumphrey NJ, Taylor V, Freeman S, Douglas MR, Bradfield PF, Young SP, Lord JM, Wakelam MJ, Bird IN, Salmon M, Buckley CD | title = Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31 | journal = FEBS Letters | volume = 450 | issue = 1–2 | pages = 77–83 | date = April 1999 | pmid = 10350061 | doi = 10.1016/s0014-5793(99)00446-9 | s2cid = 31471121 | doi-access = free }}</ref>
* [[Cbl gene]]<ref name = pmid12061819/><ref name = pmid9712732>{{cite journal | vauthors = Graham LJ, Stoica BA, Shapiro M, DeBell KE, Rellahan B, Laborda J, Bonvini E | title = Sequences surrounding the Src-homology 3 domain of phospholipase Cgamma-1 increase the domain's association with Cbl | journal = Biochemical and Biophysical Research Communications | volume = 249 | issue = 2 | pages = 537–41 | date = August 1998 | pmid = 9712732 | doi = 10.1006/bbrc.1998.9177 }}</ref>
* [[Cbl gene]]<ref name = pmid12061819/><ref name = pmid9712732>{{cite journal | vauthors = Graham LJ, Stoica BA, Shapiro M, DeBell KE, Rellahan B, Laborda J, Bonvini E | title = Sequences surrounding the Src-homology 3 domain of phospholipase Cgamma-1 increase the domain's association with Cbl | journal = Biochemical and Biophysical Research Communications | volume = 249 | issue = 2 | pages = 537–41 | date = August 1998 | pmid = 9712732 | doi = 10.1006/bbrc.1998.9177 }}</ref>
*[[CISH]]<ref name="Palmer_2015"/>
*[[CISH (gene)|CISH]]<ref name="Palmer_2015"/>
* [[Epidermal growth factor receptor]],<ref name = pmid12061819>{{cite journal | vauthors = Tvorogov D, Carpenter G | title = EGF-dependent association of phospholipase C-gamma1 with c-Cbl | journal = Experimental Cell Research | volume = 277 | issue = 1 | pages = 86–94 | date = July 2002 | pmid = 12061819 | doi = 10.1006/excr.2002.5545 }}</ref><ref name = pmid9207933>{{cite journal | vauthors = Bedrin MS, Abolafia CM, Thompson JF | title = Cytoskeletal association of epidermal growth factor receptor and associated signaling proteins is regulated by cell density in IEC-6 intestinal cells | journal = Journal of Cellular Physiology | volume = 172 | issue = 1 | pages = 126–36 | date = July 1997 | pmid = 9207933 | doi = 10.1002/(SICI)1097-4652(199707)172:1<126::AID-JCP14>3.0.CO;2-A }}</ref>
* [[Epidermal growth factor receptor]],<ref name = pmid12061819>{{cite journal | vauthors = Tvorogov D, Carpenter G | title = EGF-dependent association of phospholipase C-gamma1 with c-Cbl | journal = Experimental Cell Research | volume = 277 | issue = 1 | pages = 86–94 | date = July 2002 | pmid = 12061819 | doi = 10.1006/excr.2002.5545 }}</ref><ref name = pmid9207933>{{cite journal | vauthors = Bedrin MS, Abolafia CM, Thompson JF | title = Cytoskeletal association of epidermal growth factor receptor and associated signaling proteins is regulated by cell density in IEC-6 intestinal cells | journal = Journal of Cellular Physiology | volume = 172 | issue = 1 | pages = 126–36 | date = July 1997 | pmid = 9207933 | doi = 10.1002/(SICI)1097-4652(199707)172:1<126::AID-JCP14>3.0.CO;2-A | s2cid = 24571987 }}</ref>
* [[Eukaryotic translation elongation factor 1 alpha 1]],<ref name = pmid11886851>{{cite journal | vauthors = Chang JS, Seok H, Kwon TK, Min DS, Ahn BH, Lee YH, Suh JW, Kim JW, Iwashita S, Omori A, Ichinose S, Numata O, Seo JK, Oh YS, Suh PG | title = Interaction of elongation factor-1alpha and pleckstrin homology domain of phospholipase C-gamma 1 with activating its activity | journal = The Journal of Biological Chemistry | volume = 277 | issue = 22 | pages = 19697–702 | date = May 2002 | pmid = 11886851 | doi = 10.1074/jbc.M111206200 | doi-access = free }}</ref>
* [[Eukaryotic translation elongation factor 1 alpha 1]],<ref name = pmid11886851>{{cite journal | vauthors = Chang JS, Seok H, Kwon TK, Min DS, Ahn BH, Lee YH, Suh JW, Kim JW, Iwashita S, Omori A, Ichinose S, Numata O, Seo JK, Oh YS, Suh PG | title = Interaction of elongation factor-1alpha and pleckstrin homology domain of phospholipase C-gamma 1 with activating its activity | journal = The Journal of Biological Chemistry | volume = 277 | issue = 22 | pages = 19697–702 | date = May 2002 | pmid = 11886851 | doi = 10.1074/jbc.M111206200 | doi-access = free }}</ref>
* [[FLT1]],<ref name = pmid9398617>{{cite journal | vauthors = Cunningham SA, Arrate MP, Brock TA, Waxham MN | title = Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites | journal = Biochemical and Biophysical Research Communications | volume = 240 | issue = 3 | pages = 635–9 | date = November 1997 | pmid = 9398617 | doi = 10.1006/bbrc.1997.7719 }}</ref>
* [[FLT1]],<ref name = pmid9398617>{{cite journal | vauthors = Cunningham SA, Arrate MP, Brock TA, Waxham MN | title = Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites | journal = Biochemical and Biophysical Research Communications | volume = 240 | issue = 3 | pages = 635–9 | date = November 1997 | pmid = 9398617 | doi = 10.1006/bbrc.1997.7719 }}</ref>
* [[GAB1]],<ref name = pmid11507676>{{cite journal | vauthors = Ueno E, Haruta T, Uno T, Usui I, Iwata M, Takano A, Kawahara J, Sasaoka T, Ishibashi O, Kobayashi M | title = Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose uptake in 3T3-L1 adipocytes | journal = Hormone and Metabolic Research | volume = 33 | issue = 7 | pages = 402–6 | date = July 2001 | pmid = 11507676 | doi = 10.1055/s-2001-16227 }}</ref><ref name = pmid8596638>{{cite journal | vauthors = Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ | title = A Grb2-associated docking protein in EGF- and insulin-receptor signalling | journal = Nature | volume = 379 | issue = 6565 | pages = 560–4 | date = February 1996 | pmid = 8596638 | doi = 10.1038/379560a0 | s2cid = 4271970 }}</ref>
* [[GAB1]],<ref name = pmid11507676>{{cite journal | vauthors = Ueno E, Haruta T, Uno T, Usui I, Iwata M, Takano A, Kawahara J, Sasaoka T, Ishibashi O, Kobayashi M | title = Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose uptake in 3T3-L1 adipocytes | journal = Hormone and Metabolic Research | volume = 33 | issue = 7 | pages = 402–6 | date = July 2001 | pmid = 11507676 | doi = 10.1055/s-2001-16227 | s2cid = 9125865 }}</ref><ref name = pmid8596638>{{cite journal | vauthors = Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ | title = A Grb2-associated docking protein in EGF- and insulin-receptor signalling | journal = Nature | volume = 379 | issue = 6565 | pages = 560–4 | date = February 1996 | pmid = 8596638 | doi = 10.1038/379560a0 | bibcode = 1996Natur.379..560H | s2cid = 4271970 }}</ref>
* [[GIT1]],<ref name = pmid14523024>{{cite journal | vauthors = Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, Heller M, Aebersold R, Berk BC | title = GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor | journal = The Journal of Biological Chemistry | volume = 278 | issue = 50 | pages = 49936–44 | date = December 2003 | pmid = 14523024 | doi = 10.1074/jbc.M307317200 | doi-access = free }}</ref>
* [[GIT1]],<ref name = pmid14523024>{{cite journal | vauthors = Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, Heller M, Aebersold R, Berk BC | title = GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor | journal = The Journal of Biological Chemistry | volume = 278 | issue = 50 | pages = 49936–44 | date = December 2003 | pmid = 14523024 | doi = 10.1074/jbc.M307317200 | doi-access = free }}</ref>
* [[Grb2]],<ref name = pmid9281317>{{cite journal | vauthors = Pei Z, Maloney JA, Yang L, Williamson JR | title = A new function for phospholipase C-gamma1: coupling to the adaptor protein GRB2 | journal = Archives of Biochemistry and Biophysics | volume = 345 | issue = 1 | pages = 103–10 | date = September 1997 | pmid = 9281317 | doi = 10.1006/abbi.1997.0245 }}</ref><ref name = pmid7629168>{{cite journal | vauthors = Nel AE, Gupta S, Lee L, Ledbetter JA, Kanner SB | title = Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR | journal = The Journal of Biological Chemistry | volume = 270 | issue = 31 | pages = 18428–36 | date = August 1995 | pmid = 7629168 | doi = 10.1074/jbc.270.31.18428 | doi-access = free }}</ref><ref name = pmid10940929>{{cite journal | vauthors = Scholler JK, Perez-Villar JJ, O'Day K, Kanner SB | title = Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of phospholipase Cgamma1 | journal = European Journal of Immunology | volume = 30 | issue = 8 | pages = 2378–87 | date = August 2000 | pmid = 10940929 | doi = 10.1002/1521-4141(2000)30:8<2378::AID-IMMU2378>3.0.CO;2-E }}</ref>
* [[Grb2]],<ref name = pmid9281317>{{cite journal | vauthors = Pei Z, Maloney JA, Yang L, Williamson JR | title = A new function for phospholipase C-gamma1: coupling to the adaptor protein GRB2 | journal = Archives of Biochemistry and Biophysics | volume = 345 | issue = 1 | pages = 103–10 | date = September 1997 | pmid = 9281317 | doi = 10.1006/abbi.1997.0245 | doi-access = free }}</ref><ref name = pmid7629168>{{cite journal | vauthors = Nel AE, Gupta S, Lee L, Ledbetter JA, Kanner SB | title = Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR | journal = The Journal of Biological Chemistry | volume = 270 | issue = 31 | pages = 18428–36 | date = August 1995 | pmid = 7629168 | doi = 10.1074/jbc.270.31.18428 | doi-access = free }}</ref><ref name = pmid10940929>{{cite journal | vauthors = Scholler JK, Perez-Villar JJ, O'Day K, Kanner SB | title = Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of phospholipase Cgamma1 | journal = European Journal of Immunology | volume = 30 | issue = 8 | pages = 2378–87 | date = August 2000 | pmid = 10940929 | doi = 10.1002/1521-4141(2000)30:8<2378::AID-IMMU2378>3.0.CO;2-E | doi-access = free }}</ref>
* [[HER2/neu]],<ref name = pmid1676673>{{cite journal | vauthors = Peles E, Levy RB, Or E, Ullrich A, Yarden Y | title = Oncogenic forms of the neu/HER2 tyrosine kinase are permanently coupled to phospholipase C gamma | journal = The EMBO Journal | volume = 10 | issue = 8 | pages = 2077–86 | date = August 1991 | pmid = 1676673 | pmc = 452891 | doi = 10.1002/j.1460-2075.1991.tb07739.x}}</ref><ref name = pmid1683701>{{cite journal | vauthors = Arteaga CL, Johnson MD, Todderud G, Coffey RJ, Carpenter G, Page DL | title = Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 23 | pages = 10435–9 | date = December 1991 | pmid = 1683701 | pmc = 52943 | doi = 10.1073/pnas.88.23.10435 }}</ref>
* [[HER2/neu]],<ref name = pmid1676673>{{cite journal | vauthors = Peles E, Levy RB, Or E, Ullrich A, Yarden Y | title = Oncogenic forms of the neu/HER2 tyrosine kinase are permanently coupled to phospholipase C gamma | journal = The EMBO Journal | volume = 10 | issue = 8 | pages = 2077–86 | date = August 1991 | pmid = 1676673 | pmc = 452891 | doi = 10.1002/j.1460-2075.1991.tb07739.x}}</ref><ref name = pmid1683701>{{cite journal | vauthors = Arteaga CL, Johnson MD, Todderud G, Coffey RJ, Carpenter G, Page DL | title = Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 23 | pages = 10435–9 | date = December 1991 | pmid = 1683701 | pmc = 52943 | doi = 10.1073/pnas.88.23.10435 | bibcode = 1991PNAS...8810435A | doi-access = free }}</ref>
* [[IRS2]],<ref name = pmid9535722>{{cite journal | vauthors = Sozzani P, Hasan L, Séguélas MH, Caput D, Ferrara P, Pipy B, Cambon C | title = IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production | journal = Biochemical and Biophysical Research Communications | volume = 244 | issue = 3 | pages = 665–70 | date = March 1998 | pmid = 9535722 | doi = 10.1006/bbrc.1998.8314 }}</ref>
* [[IRS2]],<ref name = pmid9535722>{{cite journal | vauthors = Sozzani P, Hasan L, Séguélas MH, Caput D, Ferrara P, Pipy B, Cambon C | title = IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production | journal = Biochemical and Biophysical Research Communications | volume = 244 | issue = 3 | pages = 665–70 | date = March 1998 | pmid = 9535722 | doi = 10.1006/bbrc.1998.8314 }}</ref>
* [[ITK (gene)|ITK]],<ref name = pmid10586033>{{cite journal | vauthors = Perez-Villar JJ, Kanner SB | title = Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes | journal = Journal of Immunology | volume = 163 | issue = 12 | pages = 6435–41 | date = December 1999 | pmid = 10586033 | doi = }}</ref><ref name = pmid12163161>{{cite journal | vauthors = Hao S, August A | title = The proline rich region of the Tec homology domain of ITK regulates its activity | journal = FEBS Letters | volume = 525 | issue = 1–3 | pages = 53–8 | date = August 2002 | pmid = 12163161 | doi = 10.1016/s0014-5793(02)03066-1 | s2cid = 21541455 }}</ref>
* [[ITK (gene)|ITK]],<ref name = pmid10586033>{{cite journal | vauthors = Perez-Villar JJ, Kanner SB | title = Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes | journal = Journal of Immunology | volume = 163 | issue = 12 | pages = 6435–41 | date = December 1999 | doi = 10.4049/jimmunol.163.12.6435 | pmid = 10586033 | doi-access = free }}</ref><ref name = pmid12163161>{{cite journal | vauthors = Hao S, August A | title = The proline rich region of the Tec homology domain of ITK regulates its activity | journal = FEBS Letters | volume = 525 | issue = 1–3 | pages = 53–8 | date = August 2002 | pmid = 12163161 | doi = 10.1016/s0014-5793(02)03066-1 | s2cid = 21541455 | doi-access = free }}</ref>
* [[KHDRBS1]],<ref name = pmid11960376>{{cite journal | vauthors = Oneyama C, Nakano H, Sharma SV | title = UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug | journal = Oncogene | volume = 21 | issue = 13 | pages = 2037–50 | date = March 2002 | pmid = 11960376 | doi = 10.1038/sj.onc.1205271 | doi-access = free }}</ref><ref name = pmid9743338>{{cite journal | vauthors = Jabado N, Jauliac S, Pallier A, Bernard F, Fischer A, Hivroz C | title = Sam68 association with p120GAP in CD4+ T cells is dependent on CD4 molecule expression | journal = Journal of Immunology | volume = 161 | issue = 6 | pages = 2798–803 | date = September 1998 | pmid = 9743338 | doi = }}</ref><ref name = pmid10467411>{{cite journal | vauthors = Shen Z, Batzer A, Koehler JA, Polakis P, Schlessinger J, Lydon NB, Moran MF | title = Evidence for SH3 domain directed binding and phosphorylation of Sam68 by Src | journal = Oncogene | volume = 18 | issue = 33 | pages = 4647–53 | date = August 1999 | pmid = 10467411 | doi = 10.1038/sj.onc.1203079 | doi-access = free }}</ref>
* [[KHDRBS1]],<ref name = pmid11960376>{{cite journal | vauthors = Oneyama C, Nakano H, Sharma SV | title = UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug | journal = Oncogene | volume = 21 | issue = 13 | pages = 2037–50 | date = March 2002 | pmid = 11960376 | doi = 10.1038/sj.onc.1205271 | doi-access = free }}</ref><ref name = pmid9743338>{{cite journal | vauthors = Jabado N, Jauliac S, Pallier A, Bernard F, Fischer A, Hivroz C | title = Sam68 association with p120GAP in CD4+ T cells is dependent on CD4 molecule expression | journal = Journal of Immunology | volume = 161 | issue = 6 | pages = 2798–803 | date = September 1998 | doi = 10.4049/jimmunol.161.6.2798 | pmid = 9743338 | doi-access = free }}</ref><ref name = pmid10467411>{{cite journal | vauthors = Shen Z, Batzer A, Koehler JA, Polakis P, Schlessinger J, Lydon NB, Moran MF | title = Evidence for SH3 domain directed binding and phosphorylation of Sam68 by Src | journal = Oncogene | volume = 18 | issue = 33 | pages = 4647–53 | date = August 1999 | pmid = 10467411 | doi = 10.1038/sj.onc.1203079 | doi-access = free }}</ref>
* [[Linker of activated T cells]],<ref name = pmid9729044>{{cite journal | vauthors = Zhang W, Trible RP, Samelson LE | title = LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation | journal = Immunity | volume = 9 | issue = 2 | pages = 239–46 | date = August 1998 | pmid = 9729044 | doi = 10.1016/s1074-7613(00)80606-8 }}</ref><ref name = pmid11368773>{{cite journal | vauthors = Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A | title = Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells | journal = The Biochemical Journal | volume = 356 | issue = Pt 2 | pages = 461–71 | date = June 2001 | pmid = 11368773 | pmc = 1221857 | doi = 10.1042/0264-6021:3560461 }}</ref><ref name = pmid9489702>{{cite journal | vauthors = Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE | title = LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation | journal = Cell | volume = 92 | issue = 1 | pages = 83–92 | date = January 1998 | pmid = 9489702 | doi = 10.1016/S0092-8674(00)80901-0 | s2cid = 1806525 }}</ref>
* [[Linker of activated T cells]],<ref name = pmid9729044>{{cite journal | vauthors = Zhang W, Trible RP, Samelson LE | title = LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation | journal = Immunity | volume = 9 | issue = 2 | pages = 239–46 | date = August 1998 | pmid = 9729044 | doi = 10.1016/s1074-7613(00)80606-8 | doi-access = free }}</ref><ref name = pmid11368773>{{cite journal | vauthors = Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A | title = Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells | journal = The Biochemical Journal | volume = 356 | issue = Pt 2 | pages = 461–71 | date = June 2001 | pmid = 11368773 | pmc = 1221857 | doi = 10.1042/0264-6021:3560461 }}</ref><ref name = pmid9489702>{{cite journal | vauthors = Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE | title = LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation | journal = Cell | volume = 92 | issue = 1 | pages = 83–92 | date = January 1998 | pmid = 9489702 | doi = 10.1016/S0092-8674(00)80901-0 | s2cid = 1806525 | doi-access = free }}</ref>
* [[Lymphocyte cytosolic protein 2]],<ref name = pmid11390650>{{cite journal | vauthors = Yablonski D, Kadlecek T, Weiss A | title = Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT | journal = Molecular and Cellular Biology | volume = 21 | issue = 13 | pages = 4208–18 | date = July 2001 | pmid = 11390650 | pmc = 87082 | doi = 10.1128/MCB.21.13.4208-4218.2001 }}</ref>
* [[Lymphocyte cytosolic protein 2]],<ref name = pmid11390650>{{cite journal | vauthors = Yablonski D, Kadlecek T, Weiss A | title = Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT | journal = Molecular and Cellular Biology | volume = 21 | issue = 13 | pages = 4208–18 | date = July 2001 | pmid = 11390650 | pmc = 87082 | doi = 10.1128/MCB.21.13.4208-4218.2001 }}</ref>
* [[PDGFRA]],<ref name = pmid7535778>{{cite journal | vauthors = Eriksson A, Nånberg E, Rönnstrand L, Engström U, Hellman U, Rupp E, Carpenter G, Heldin CH, Claesson-Welsh L | title = Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors | journal = The Journal of Biological Chemistry | volume = 270 | issue = 13 | pages = 7773–81 | date = March 1995 | pmid = 7535778 | doi = 10.1074/jbc.270.13.7773 | doi-access = free }}</ref>
* [[PDGFRA]],<ref name = pmid7535778>{{cite journal | vauthors = Eriksson A, Nånberg E, Rönnstrand L, Engström U, Hellman U, Rupp E, Carpenter G, Heldin CH, Claesson-Welsh L | title = Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors | journal = The Journal of Biological Chemistry | volume = 270 | issue = 13 | pages = 7773–81 | date = March 1995 | pmid = 7535778 | doi = 10.1074/jbc.270.13.7773 | doi-access = free }}</ref>
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* [[SOS1]],<ref name = pmid10940929/><ref name = pmid10913276>{{cite journal | vauthors = Kim MJ, Chang JS, Park SK, Hwang JI, Ryu SH, Suh PG | title = Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-gamma1 | journal = Biochemistry | volume = 39 | issue = 29 | pages = 8674–82 | date = July 2000 | pmid = 10913276 | doi = 10.1021/bi992558t }}</ref>
* [[SOS1]],<ref name = pmid10940929/><ref name = pmid10913276>{{cite journal | vauthors = Kim MJ, Chang JS, Park SK, Hwang JI, Ryu SH, Suh PG | title = Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-gamma1 | journal = Biochemistry | volume = 39 | issue = 29 | pages = 8674–82 | date = July 2000 | pmid = 10913276 | doi = 10.1021/bi992558t }}</ref>
* [[TUB (gene)|TUB]],<ref name = pmid10455176>{{cite journal | vauthors = Kapeller R, Moriarty A, Strauss A, Stubdal H, Theriault K, Siebert E, Chickering T, Morgenstern JP, Tartaglia LA, Lillie J | title = Tyrosine phosphorylation of tub and its association with Src homology 2 domain-containing proteins implicate tub in intracellular signaling by insulin | journal = The Journal of Biological Chemistry | volume = 274 | issue = 35 | pages = 24980–6 | date = August 1999 | pmid = 10455176 | doi = 10.1074/jbc.274.35.24980 | doi-access = free }}</ref>
* [[TUB (gene)|TUB]],<ref name = pmid10455176>{{cite journal | vauthors = Kapeller R, Moriarty A, Strauss A, Stubdal H, Theriault K, Siebert E, Chickering T, Morgenstern JP, Tartaglia LA, Lillie J | title = Tyrosine phosphorylation of tub and its association with Src homology 2 domain-containing proteins implicate tub in intracellular signaling by insulin | journal = The Journal of Biological Chemistry | volume = 274 | issue = 35 | pages = 24980–6 | date = August 1999 | pmid = 10455176 | doi = 10.1074/jbc.274.35.24980 | doi-access = free }}</ref>
* [[TrkA]],<ref name = pmid1715690>{{cite journal | vauthors = Ohmichi M, Decker SJ, Pang L, Saltiel AR | title = Nerve growth factor binds to the 140 kd trk proto-oncogene product and stimulates its association with the src homology domain of phospholipase C gamma 1 | journal = Biochemical and Biophysical Research Communications | volume = 179 | issue = 1 | pages = 217–23 | date = August 1991 | pmid = 1715690 | doi = 10.1016/0006-291x(91)91357-i | hdl = 2027.42/29169 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/29169/1/0000215.pdf }}</ref><ref name = pmid9856458>{{cite journal | vauthors = Qian X, Riccio A, Zhang Y, Ginty DD | title = Identification and characterization of novel substrates of Trk receptors in developing neurons | journal = Neuron | volume = 21 | issue = 5 | pages = 1017–29 | date = November 1998 | pmid = 9856458 | doi = 10.1016/s0896-6273(00)80620-0 | s2cid = 12354383 }}</ref><ref name = pmid10092678>{{cite journal | vauthors = Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM | title = The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 14 | pages = 9861–70 | date = April 1999 | pmid = 10092678 | doi = 10.1074/jbc.274.14.9861 | doi-access = free }}</ref><ref name = pmid10708759>{{cite journal | vauthors = Koch A, Mancini A, Stefan M, Niedenthal R, Niemann H, Tamura T | title = Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop | journal = FEBS Letters | volume = 469 | issue = 1 | pages = 72–6 | date = March 2000 | pmid = 10708759 | doi = 10.1016/s0014-5793(00)01242-4 | s2cid = 28312468 }}</ref>
* [[TrkA]],<ref name = pmid1715690>{{cite journal | vauthors = Ohmichi M, Decker SJ, Pang L, Saltiel AR | title = Nerve growth factor binds to the 140 kd trk proto-oncogene product and stimulates its association with the src homology domain of phospholipase C gamma 1 | journal = Biochemical and Biophysical Research Communications | volume = 179 | issue = 1 | pages = 217–23 | date = August 1991 | pmid = 1715690 | doi = 10.1016/0006-291x(91)91357-i | hdl = 2027.42/29169 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/29169/1/0000215.pdf | hdl-access = free }}</ref><ref name = pmid9856458>{{cite journal | vauthors = Qian X, Riccio A, Zhang Y, Ginty DD | title = Identification and characterization of novel substrates of Trk receptors in developing neurons | journal = Neuron | volume = 21 | issue = 5 | pages = 1017–29 | date = November 1998 | pmid = 9856458 | doi = 10.1016/s0896-6273(00)80620-0 | s2cid = 12354383 | doi-access = free }}</ref><ref name = pmid10092678>{{cite journal | vauthors = Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM | title = The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 14 | pages = 9861–70 | date = April 1999 | pmid = 10092678 | doi = 10.1074/jbc.274.14.9861 | doi-access = free }}</ref><ref name = pmid10708759>{{cite journal | vauthors = Koch A, Mancini A, Stefan M, Niedenthal R, Niemann H, Tamura T | title = Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop | journal = FEBS Letters | volume = 469 | issue = 1 | pages = 72–6 | date = March 2000 | pmid = 10708759 | doi = 10.1016/s0014-5793(00)01242-4 | s2cid = 28312468 | doi-access = free }}</ref>
* [[TrkB]],<ref name = pmid10092678/><ref name = pmid12074588>{{cite journal | vauthors = Suzuki S, Mizutani M, Suzuki K, Yamada M, Kojima M, Hatanaka H, Koizumi S | title = Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor | journal = Biochemical and Biophysical Research Communications | volume = 294 | issue = 5 | pages = 1087–92 | date = June 2002 | pmid = 12074588 | doi = 10.1016/S0006-291X(02)00606-X }}</ref>
* [[TrkB]],<ref name = pmid10092678/><ref name = pmid12074588>{{cite journal | vauthors = Suzuki S, Mizutani M, Suzuki K, Yamada M, Kojima M, Hatanaka H, Koizumi S | title = Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor | journal = Biochemical and Biophysical Research Communications | volume = 294 | issue = 5 | pages = 1087–92 | date = June 2002 | pmid = 12074588 | doi = 10.1016/S0006-291X(02)00606-X }}</ref>
* [[VAV1]],<ref name = pmid9891995>{{cite journal | vauthors = Bertagnolo V, Marchisio M, Volinia S, Caramelli E, Capitani S | title = Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells | journal = FEBS Letters | volume = 441 | issue = 3 | pages = 480–4 | date = December 1998 | pmid = 9891995 | doi = 10.1016/s0014-5793(98)01593-2 | s2cid = 38371954 }}</ref> and
* [[VAV1]],<ref name = pmid9891995>{{cite journal | vauthors = Bertagnolo V, Marchisio M, Volinia S, Caramelli E, Capitani S | title = Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells | journal = FEBS Letters | volume = 441 | issue = 3 | pages = 480–4 | date = December 1998 | pmid = 9891995 | doi = 10.1016/s0014-5793(98)01593-2 | s2cid = 38371954 | doi-access = free }}</ref> and
* [[Wiskott-Aldrich syndrome protein]].<ref name = pmid8805332>{{cite journal | vauthors = Banin S, Truong O, Katz DR, Waterfield MD, Brickell PM, Gout I | title = Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases | journal = Current Biology | volume = 6 | issue = 8 | pages = 981–8 | date = August 1996 | pmid = 8805332 | doi = 10.1016/s0960-9822(02)00642-5 | s2cid = 162267 }}</ref><ref name = pmid8824280>{{cite journal | vauthors = Finan PM, Soames CJ, Wilson L, Nelson DL, Stewart DM, Truong O, Hsuan JJ, Kellie S | title = Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains | journal = The Journal of Biological Chemistry | volume = 271 | issue = 42 | pages = 26291–5 | date = October 1996 | pmid = 8824280 | doi = 10.1074/jbc.271.42.26291 | doi-access = free }}</ref>
* [[Wiskott-Aldrich syndrome protein]].<ref name = pmid8805332>{{cite journal | vauthors = Banin S, Truong O, Katz DR, Waterfield MD, Brickell PM, Gout I | title = Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases | journal = Current Biology | volume = 6 | issue = 8 | pages = 981–8 | date = August 1996 | pmid = 8805332 | doi = 10.1016/s0960-9822(02)00642-5 | s2cid = 162267 | doi-access = free | bibcode = 1996CBio....6..981B }}</ref><ref name = pmid8824280>{{cite journal | vauthors = Finan PM, Soames CJ, Wilson L, Nelson DL, Stewart DM, Truong O, Hsuan JJ, Kellie S | title = Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains | journal = The Journal of Biological Chemistry | volume = 271 | issue = 42 | pages = 26291–5 | date = October 1996 | pmid = 8824280 | doi = 10.1074/jbc.271.42.26291 | doi-access = free }}</ref>
{{Div col end}}
{{Div col end}}


Latest revision as of 00:40, 13 August 2024

PLCG1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPLCG1, NCKAP3, PLC-II, PLC1, PLC148, PLCgamma1, phospholipase C gamma 1
External IDsOMIM: 172420; MGI: 97615; HomoloGene: 1997; GeneCards: PLCG1; OMA:PLCG1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5335

18803

Ensembl

ENSG00000124181

ENSMUSG00000016933

UniProt

P19174

Q62077

RefSeq (mRNA)

NM_002660
NM_182811

NM_021280

RefSeq (protein)

NP_002651
NP_877963

NP_067255

Location (UCSC)Chr 20: 41.14 – 41.2 MbChr 2: 160.57 – 160.62 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Phospholipase C, gamma 1, also known as PLCG1 and PLCgamma1, is a protein that in humans involved in cell growth, migration, apoptosis, and proliferation. It is encoded by the PLCG1 gene[5][6] and is part of the PLC superfamily.

Function

[edit]

PLCγ1 is a cell growth factor[7][8] from the PLC superfamily. PLCγ1 is used during cell growth[7] and in cell migration[9] and apoptosis,[8] all of which are vital cell processes that, if disrupted by mutations, can cause cancerous cells to form within the body. Mutations in this protein show an increase in issues in cells regarding regulation of proliferation and their cell signaling.[7] PLCγ1 roles are also involved in neuronal actin growth, calcium signaling, and brain development.[10][8][9] It is highly regulated by multiple factors, such as PIK3, AMPK, and FAK.[8][11] It is part of the PIP3 pathway and leads to and increase in calcium in the cells. In neuronal cells, PLCγ1 is highly involved in actin cytoskeleton organization and synaptic plasticity.[10] The basic PLCγ1 pathway, as scientists currently understand it, is seen below.

PLCG1 Pathway

The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of receptor-mediated tyrosine kinase activators. For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RASGRP1 to translocate to the Golgi apparatus, where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. The receptor protein tyrosine phosphatase PTPmu (PTPRM) is capable of dephosphorylating PLCG1.[12] Two transcript variants encoding different isoforms have been found for this gene.[13]

Common to all PLC isozymes, PLCG1 consists of an N-terminal PH domain, which translocates PLC to the plasma membrane and binds PIP3;[14] four EF hands; an X and Y catalytic region comprising the TIM barrel; and a C-terminal C2 domain.[15] Specific to the PLCG isozymes is a large separation between the X and Y domains consisting of a split PH domain, tandem SH2 domains, and an SH3 domain.[15] The SH2 domains bind phosphorylated tyrosine residues on target proteins via their FLVR sequence motifs, activating the catalytic function of PLCg; and the SH3 domain binds to proline-rich sequences on the target protein.[15]

PLCG1 can be activated by receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases. For example, when activated, fibroblast growth factor receptor 1 and epidermal growth factor receptor are RTKs that have phosphorylated tyrosines, which provide docking sites for PLCG1 SH2 domains.[15] The activated RTKs phosphoylate PLCG1 at tyrosines located at position 472, 771, 775, 783, and 1254.[16] Non-receptor tyrosine kinases interact with PLCG1 in large complexes at the plasma membrane. For example, in T cells, Lck and Fyn (Src family kinases) phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) on the T-cell antigen receptor (TCR).[15] The phosphorylated ITAMs recruit ZAP-70, which phosphorylates tyrosines in LAT and SLP-76. PLCg1 binds to LAT through its n-terminal SH2 domain and to SLP-76 via its SH3 domain.[15]

Has been shown to interact with CISH which negatively regulates it by targeting it for degradation.[17] The deletion of Cish in effector T cells has been shown to augment TCR signaling and subsequent effector cytokine release, proliferation and survival. The adoptive transfer of tumor-specific effector T cells knocked out or knocked down for CISH resulted in a significant increase in functional avidity and long-term tumor immunity. There are no changes in activity or phosphorylation of Cish's purported target, STAT5 in either the presence or absence of Cish.

In vitro studies have shown signs of PLCγ1 having many cell-motility functions, however in vivo have not been able to show a physiological role for PLCγ1.[18] While PLCγ1 is well documented and easily found in the body, clear connections and roles for PLCγ1 have been difficult to find in in vivo studies. Despite this, there is still able to find links between levels of PLCγ1 and cancer patient survivability.

Cancer

[edit]

Mutations in PLCγ1 can lead to cancer cell proliferations and inhibition can lead to tumor growth.[19] PLCγ1 is involved in cell proliferation, and mutations cause it to be over expressed and help the progression of tumor cells. This aspect of PLCγ1 also helps cancer migration and metastasis away from the original tumor cells.[20][21] There is also a link between PLCγ1 and PDK, the PDK-PLCγ1 pathway, which is a vital part of cancer cell invasion.[21]

The inhibition of PLCγ1 is linked to a decrease in tumor growth and metastasis.[19][20] PLCγ1 is acting as a vital part in stopping apoptosis in cells, and thus by inhibiting PLCγ1 the body better allows programmed cell death and avoidance of tumors.[19][20] The main role found for PLCγ1 is cell growth, and this role in specific is why it is becoming more commonly studied for anti-cancer drugs.[20][21] Tissue samples from cancer patients the PLCγ1 levels are not elevated, however, regulatory factors for this proteins are lowered and that amplification of PLCγ1 is extremely high.[20] The regulatory proteins that stop PLCγ1 have been turned off by the cell, which means that while there is no increase in the physical protein PLCγ1 there is an increase in how much work it is doing - nothing is stopping it from over working itself. Studies also showed that adding new regulatory to cells in vitro helped reduce previously amplified PLCγ1.[19] This information has encouraged PLCγ1 becoming an anti-cancer drug target despite the issues that come with targeting intermembrane proteins.[19][21][22]

Interactions

[edit]

PLCG1 has been shown to interact with:

See also

[edit]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000124181 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000016933 – Ensembl, May 2017
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  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  8. ^ a b c d Lattanzio R, Piantelli M, Falasca M (September 2013). "Role of phospholipase C in cell invasion and metastasis". Advances in Biological Regulation. 53 (3): 309–18. doi:10.1016/j.jbior.2013.07.006. PMID 23925006.
  9. ^ a b Jang HJ, Suh PG, Lee YJ, Shin KJ, Cocco L, Chae YC (January 2018). "PLCγ1: Potential arbitrator of cancer progression". Advances in Biological Regulation. 67: 179–189. doi:10.1016/j.jbior.2017.11.003. PMID 29174396.
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