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Protein phosphatase 1 regulatory subunit 14A also known as CPI-17 (C-kinase potentiated Protein phosphatase-1 Inhibitor Mr = 17 kDa) is a protein that in humans is encoded by the PPP1R14Agene.[4][5][6]
Function
CPI-17 is a phosphorylation-dependent inhibitor protein of smooth muscle myosin phosphatase, discovered in pig aortic homogenates. Phosphorylation of the Thr-38 residue converts the protein into a potent inhibitor for myosin phosphatase. A single phosphorylation of CPI-17 at Thr-38 triggers a global conformational change that causes re-alignment of four helices. Multiple kinases are identified to phosphorylate CPI-17, such as PKC, ROCK, PKN, ZIPK, ILK, and PAK. Agonist stimulation of smooth muscle enhances CPI-17 phosphorylation mainly through PKC and ROCK. Myosin phosphatase inhibition increases myosin phosphorylation and smooth muscle contraction in the absence of increased intracellular Ca2+ concentration. This phenomenon is known as Ca2+ sensitization, which occurs in response to agonist stimulation of smooth muscle. In Purkinje neuron, CPI-17 is involved in long-term synaptic depression.
CPI-17 is up-regulated some cancer cells, and causes hyperphosphorylation of tumor suppressor merlin/NF2.[7][6] In prostate cancer, CPI-17 expressions are reported to be associated with GWAS risk SNP rs7247241 T allele and increase cell proliferation. [8]
^Yamawaki K, Ito M, Machida H, Moriki N, Okamoto R, Isaka N, et al. (July 2001). "Identification of human CPI-17, an inhibitory phosphoprotein for myosin phosphatase". Biochemical and Biophysical Research Communications. 285 (4): 1040–1045. doi:10.1006/bbrc.2001.5290. PMID11467857.
Hamaguchi T, Ito M, Feng J, Seko T, Koyama M, Machida H, et al. (August 2000). "Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N". Biochemical and Biophysical Research Communications. 274 (3): 825–830. doi:10.1006/bbrc.2000.3225. PMID10924361.
Li Z, Yu L, Zhang Y, Gao J, Zhang P, Wan B, et al. (2002). "Identification of human, mouse and rat PPP1R14A, protein phosphatase-1 inhibitor subunit 14A, & mapping human PPP1R14A to chromosome 19q13.13-q13.2". Molecular Biology Reports. 28 (2): 91–101. doi:10.1023/A:1017998029053. PMID11931393. S2CID37230257.
Zemlickova E, Johannes FJ, Aitken A, Dubois T (March 2004). "Association of CPI-17 with protein kinase C and casein kinase I". Biochemical and Biophysical Research Communications. 316 (1): 39–47. doi:10.1016/j.bbrc.2004.02.014. PMID15003508.
Kolosova IA, Ma SF, Adyshev DM, Wang P, Ohba M, Natarajan V, et al. (November 2004). "Role of CPI-17 in the regulation of endothelial cytoskeleton". American Journal of Physiology. Lung Cellular and Molecular Physiology. 287 (5): L970–L980. doi:10.1152/ajplung.00398.2003. PMID15234908.
Morin C, Sirois M, Echave V, Gomes MM, Rousseau E (May 2007). "Epoxyeicosatrienoic acid relaxing effects involve Ca2+-activated K+ channel activation and CPI-17 dephosphorylation in human bronchi". American Journal of Respiratory Cell and Molecular Biology. 36 (5): 633–641. doi:10.1165/rcmb.2006-0281OC. PMID17237191.
