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{{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]].<ref name="pmid= 8720121">{{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= }}</ref><ref name= "pmid11467857">{{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 }}</ref><ref name="entrez">{{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 = }}</ref>
== Function ==
CPI-17 is a [[phosphorylation]]-dependent inhibitor protein of smooth muscle myosin [[phosphatase]], discovered in pig aortic homogenetes. Phosphorylation of the [[threonine|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 [[Protein kinase C|PKC]], [[Rho kinase|ROCK]], [[Protein kinase|PKN]], [[ZIPK]], [[integrin-linked kinase|ILK]], and [[p21 activated kinases|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 Ca<sup>2+</sup> concentration. This phenomenon is known as Ca<sup>2+</sup> 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.<ref name="pmid= 19846560">{{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  }}</ref><ref name="entrez"/>
==References==
{{reflist}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading | citations =
*{{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=  }}
*{{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}}
}}
{{refend}}
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Protein phosphatase 1, regulatory (inhibitor) subunit 14A
| HGNCid = 14871
| Symbol = PPP1R14A
| AltSymbols =; CPI-17; PPP1INL
| OMIM = 608153
| ECnumber = 
| Homologene = 12267
| MGIid = 1931139
| Function = {{GNF_GO|id=GO:0004864 |text = protein phosphatase inhibitor activity}}
| Component =
| Process =
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 94274
    | Hs_Ensembl = ENSG00000167641
    | Hs_RefseqProtein = NP_150281
    | Hs_RefseqmRNA = NM_033256
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 19
    | Hs_GenLoc_start = 43433717
    | Hs_GenLoc_end = 43439071
    | Hs_Uniprot = Q96A00
    | Mm_EntrezGene = 68458
    | Mm_Ensembl = ENSMUSG00000037166
    | Mm_RefseqmRNA = NM_026731
    | Mm_RefseqProtein = NP_081007
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 7
    | Mm_GenLoc_start = 28998072
    | Mm_GenLoc_end = 29002151
    | Mm_Uniprot = Q91VC7
  }}
}}
'''Protein phosphatase 1, regulatory (inhibitor) subunit 14A''', also known as '''PPP1R14A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PPP1R14A protein phosphatase 1, regulatory (inhibitor) subunit 14A| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=94274| accessdate = }}</ref>
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text = PPP1R14A is a phosphorylation-dependent inhibitor of smooth muscle myosin phosphatase (see MIM 603768). Inhibition leads to increased myosin phosphorylation and enhances smooth muscle contraction in the absence of increased intracellular Ca(2+) concentration.[supplied by OMIM]<ref name="entrez">{{cite web | title = Entrez Gene: PPP1R14A protein phosphatase 1, regulatory (inhibitor) subunit 14A| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=94274| accessdate = }}</ref>
}}
==References==
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Eto M, Ohmori T, Suzuki M, ''et al.'' |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=  }}
*{{cite journal  | author=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=  }}
*{{cite journal  | author=Koyama M, Ito M, Feng J, ''et al.'' |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=  }}
*{{cite journal  | author=Hamaguchi T, Ito M, Feng J, ''et al.'' |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  | author=Yamawaki K, Ito M, Machida H, ''et al.'' |title=Identification of human CPI-17, an inhibitory phosphoprotein for myosin phosphatase. |journal=Biochem. Biophys. Res. Commun. |volume=285 |issue= 4 |pages= 1040-5 |year= 2001 |pmid= 11467857 |doi= 10.1006/bbrc.2001.5290 }}
*{{cite journal  | author=Li Z, Yu L, Zhang Y, ''et al.'' |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=  }}
*{{cite journal  | author=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=  }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |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 }}
*{{cite journal  | author=Liu QR, Zhang PW, Lin Z, ''et al.'' |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 }}
*{{cite journal  | author=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  | author=Kolosova IA, Ma SF, Adyshev DM, ''et al.'' |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  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |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 }}
*{{cite journal  | author=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  | author=Morin C, Sirois M, Echave V, ''et al.'' |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  | author=Lartey J, Smith M, Pawade J, ''et al.'' |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 }}
}}
{{refend}}


{{protein-stub}}
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Latest revision as of 18:33, 7 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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]

References

  1. ↑ 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. PMID 8720121.
  2. ↑ 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. PMID 11467857.
  3. ↑ 3.0 3.1 "Entrez Gene: PPP1R14A protein phosphatase 1, regulatory (inhibitor) subunit 14A".
  4. ↑ Eto M; Ohmori, T; Suzuki, M; Furuya, K; Morita, F (2009). "Regulation of Cellular Protein Phosphatase-1 (PP1) by Phosphorylation of the CPI-17 Family, C-kinase-activated PP1 Inhibitors". J. Biol. Chem. 284 (51): 35273–7. doi:10.1074/jbc.R109.059972. PMC 2790955. PMID 19846560.

Further reading



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