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 homogenetes. 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.
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Eto M, Ohmori T, Suzuki M, et al. (1996). "A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization". J. Biochem. 118 (6): 1104–7. doi:10.1093/oxfordjournals.jbchem.a124993. PMID8720121.
^Yamawaki K, Ito M, Machida H, Moriki N, Okamoto R, Isaka N, Shimpo H, Kohda A, Okumura K, Hartshorne DJ, Nakano T (Jul 2001). "Identification of human CPI-17, an inhibitory phosphoprotein for myosin phosphatase". Biochem Biophys Res Commun. 285 (4): 1040–5. doi:10.1006/bbrc.2001.5290. PMID11467857.
Eto M, Ohmori T, Suzuki M, et al. (1996). "A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization". J. Biochem. 118 (6): 1104–7. doi:10.1093/oxfordjournals.jbchem.a124993. PMID8720121.
Eto M, Senba S, Morita F, Yazawa M (1997). "Molecular cloning of a novel phosphorylation-dependent inhibitory protein of protein phosphatase-1 (CPI17) in smooth muscle: its specific localization in smooth muscle". FEBS Lett. 410 (2–3): 356–60. doi:10.1016/S0014-5793(97)00657-1. PMID9237662.
Koyama M, Ito M, Feng J, et al. (2000). "Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase". FEBS Lett. 475 (3): 197–200. doi:10.1016/S0014-5793(00)01654-9. PMID10869555.
Hamaguchi T, Ito M, Feng J, et al. (2000). "Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N". Biochem. Biophys. Res. Commun. 274 (3): 825–30. doi:10.1006/bbrc.2000.3225. PMID10924361.
Li Z, Yu L, Zhang Y, 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". Mol. Biol. Rep. 28 (2): 91–101. doi:10.1023/A:1017998029053. PMID11931393.
Dubois T, Howell S, Zemlickova E, Aitken A (2002). "Identification of casein kinase Ialpha interacting protein partners". FEBS Lett. 517 (1–3): 167–71. doi:10.1016/S0014-5793(02)02614-5. PMID12062430.
Zemlickova E, Johannes FJ, Aitken A, Dubois T (2004). "Association of CPI-17 with protein kinase C and casein kinase I". Biochem. Biophys. Res. Commun. 316 (1): 39–47. doi:10.1016/j.bbrc.2004.02.014. PMID15003508.
Kolosova IA, Ma SF, Adyshev DM, et al. (2004). "Role of CPI-17 in the regulation of endothelial cytoskeleton". Am. J. Physiol. Lung Cell Mol. Physiol. 287 (5): L970–80. doi:10.1152/ajplung.00398.2003. PMID15234908.
