| 释义 |
- Function
- Clinical significance
- References
- Further reading
{{Infobox_gene}}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 PPP1R14A gene.[1][2][3] 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. There are three homologues of CPI-17: - Phosphatase Holoenzyme Inhibitor (PHI: PPP1R14B),
- Kinase Enhanced Phosphatase Inhibitor (KEPI: PPP1R14C), and
- Gastric-Brain Phosphatase Inhibitor (GBPI: PPP1R14D).
Clinical significance CPI-17 is up-regulated some cancer cells, and causes hyperphosphorylation of tumor suppressor merlin/NF2.[4][3] References1. ^{{cite journal |vauthors=Eto M, Ohmori T, Suzuki M, etal |title=A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization. |journal=J. Biochem. |volume=118 |issue= 6 |pages= 1104–7 |year= 1996 |pmid= 8720121 |doi= 10.1093/oxfordjournals.jbchem.a124993}}
2. ^{{cite journal |vauthors=Yamawaki K, Ito M, Machida H, Moriki N, Okamoto R, Isaka N, Shimpo H, Kohda A, Okumura K, Hartshorne DJ, Nakano T | title = Identification of human CPI-17, an inhibitory phosphoprotein for myosin phosphatase | journal = Biochem Biophys Res Commun | volume = 285 | issue = 4 | pages = 1040–5 |date=Jul 2001 | pmid = 11467857 | pmc = | doi = 10.1006/bbrc.2001.5290 }}
3. ^1 {{cite web | title = Entrez Gene: PPP1R14A protein phosphatase 1, regulatory (inhibitor) subunit 14A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=94274| accessdate = }}
4. ^{{cite journal | author = Eto M |title=Regulation of Cellular Protein Phosphatase-1 (PP1) by Phosphorylation of the CPI-17 Family, C-kinase-activated PP1 Inhibitors |journal=J. Biol. Chem. |volume=284 |issue= 51 |pages= 35273–7 |year= 2009 |pmid= 19846560 |doi= 10.1074/jbc.R109.059972| last2 = Ohmori | first2 = T | last3 = Suzuki | first3 = M | last4 = Furuya | first4 = K | last5 = Morita | first5 = F | pmc = 2790955 }}
Further reading{{refbegin | 2}}- {{cite journal |vauthors=Eto M, Ohmori T, Suzuki M, etal |title=A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization |journal=J. Biochem. |volume=118 |issue= 6 |pages= 1104–7 |year= 1996 |pmid= 8720121 |doi= 10.1093/oxfordjournals.jbchem.a124993}}
- {{cite journal |vauthors=Eto M, Senba S, Morita F, Yazawa M |title=Molecular cloning of a novel phosphorylation-dependent inhibitory protein of protein phosphatase-1 (CPI17) in smooth muscle: its specific localization in smooth muscle |journal=FEBS Lett. |volume=410 |issue= 2–3 |pages= 356–60 |year= 1997 |pmid= 9237662 |doi=10.1016/S0014-5793(97)00657-1 }}
- {{cite journal |vauthors=Koyama M, Ito M, Feng J, etal |title=Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase |journal=FEBS Lett. |volume=475 |issue= 3 |pages= 197–200 |year= 2000 |pmid= 10869555 |doi=10.1016/S0014-5793(00)01654-9 }}
- {{cite journal |vauthors=Hamaguchi T, Ito M, Feng J, etal |title=Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N |journal=Biochem. Biophys. Res. Commun. |volume=274 |issue= 3 |pages= 825–30 |year= 2000 |pmid= 10924361 |doi= 10.1006/bbrc.2000.3225 }}
- {{cite journal |vauthors=Li Z, Yu L, Zhang Y, etal |title=Identification of human, mouse and rat PPP1R14A, protein phosphatase-1 inhibitor subunit 14A, & mapping human PPP1R14A to chromosome 19q13.13-q13.2 |journal=Mol. Biol. Rep. |volume=28 |issue= 2 |pages= 91–101 |year= 2002 |pmid= 11931393 |doi=10.1023/A:1017998029053 }}
- {{cite journal |vauthors=Dubois T, Howell S, Zemlickova E, Aitken A |title=Identification of casein kinase Ialpha interacting protein partners |journal=FEBS Lett. |volume=517 |issue= 1–3 |pages= 167–71 |year= 2002 |pmid= 12062430 |doi=10.1016/S0014-5793(02)02614-5 }}
- {{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
- {{cite journal |vauthors=Liu QR, Zhang PW, Lin Z, etal |title=GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA |journal=Biochem. J. |volume=377 |issue= Pt 1 |pages= 171–81 |year= 2004 |pmid= 12974676 |doi= 10.1042/BJ20030128 | pmc=1223837 }}
- {{cite journal | author=Eto, M., Kitazawa, T., and Brautigan, D.L. |title=Phosphoprotein inhibitor CPI-17 specificity depends on allosteric regulation of protein phosphatase-1 by regulatory subunits |journal=Proc. Natl. Acad. Sci. USA |volume=101 |issue= 24 |pages= 8888–93 |year= 2004 |pmid= 15184667 |doi=10.1073/pnas.0307812101 | pmc=428442 }}
- {{cite journal |vauthors=Zemlickova E, Johannes FJ, Aitken A, Dubois T |title=Association of CPI-17 with protein kinase C and casein kinase I |journal=Biochem. Biophys. Res. Commun. |volume=316 |issue= 1 |pages= 39–47 |year= 2004 |pmid= 15003508 |doi= 10.1016/j.bbrc.2004.02.014 }}
- {{cite journal |vauthors=Kolosova IA, Ma SF, Adyshev DM, etal |title=Role of CPI-17 in the regulation of endothelial cytoskeleton |journal=Am. J. Physiol. Lung Cell Mol. Physiol. |volume=287 |issue= 5 |pages= L970–80 |year= 2004 |pmid= 15234908 |doi= 10.1152/ajplung.00398.2003 }}
- {{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
- {{cite journal |vauthors=Jin H, Sperka T, Herrlich P, Morrison H |title=Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase |journal=Nature |volume=442 |issue= 7102 |pages= 576–9 |year= 2006 |pmid= 16885985 |doi= 10.1038/nature04856 }}
- {{cite journal |vauthors=Morin C, Sirois M, Echave V, etal |title=Epoxyeicosatrienoic acid relaxing effects involve Ca2+-activated K+ channel activation and CPI-17 dephosphorylation in human bronchi |journal=Am. J. Respir. Cell Mol. Biol. |volume=36 |issue= 5 |pages= 633–41 |year= 2007 |pmid= 17237191 |doi= 10.1165/rcmb.2006-0281OC }}
- {{cite journal |vauthors=Lartey J, Smith M, Pawade J, etal |title=Up-regulation of myometrial RHO effector proteins (PKN1 and DIAPH1) and CPI-17 (PPP1R14A) phosphorylation in human pregnancy is associated with increased GTP-RHOA in spontaneous preterm labor |journal=Biol. Reprod. |volume=76 |issue= 6 |pages= 971–82 |year= 2007 |pmid= 17301291 |doi= 10.1095/biolreprod.106.058982 }}
- {{cite journal |author1=Eto M. |author2=Kitazawa T. |title=Phosphorylation-induced conformational switching of CPI-17 produces a potent myosin phosphatase inhibitor |journal=Structure |volume=15 |issue= 12 |pages= 1591–602 |year= 2007 |pmid= 18073109 |doi=10.1016/j.str.2007.10.014 | pmc=2217667 |display-authors=etal}}
- {{cite journal | author=Dimopoulous, G. J., Semba, S.|title=Ca2+-Dependent Rapid Ca2+ Sensitization of Contraction in Arterial Smooth Muscle |journal=Circ. Res. |volume=100 |issue= 1 |pages= 121–29 |year= 2007 |pmid= 17158339 |doi=10.1161/01.RES.0000253902.90489.df | pmc=2212616 |display-authors=etal}}
- {{cite journal | author=Kim, J.I., Young, G.D.|title=Expression of CPI-17 in smooth muscle during embryonic development and in neointimal lesion formation |journal=Histochem. Cell Biol. |volume=132 |issue= 2 |pages= 191–8 |year= 2009 |pmid= 19437030 |doi=10.1007/s00418-009-0604-2 | pmc=2878480 |display-authors=etal}}
- {{cite journal | author=Kitazawa, T., Semba, S.|title=Nitric oxide-induced biphasic mechanism of vascular relaxation via dephosphorylation of CPI-17 and MYPT1 |journal=J. Physiol. |volume=587 |issue= Pt14 |pages= 3587–603 |year= 2009 |pmid= 19470783 |doi=10.1113/jphysiol.2009.172189 | pmc=2742283 |display-authors=etal}}
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