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PPP1R14A

From Wikipedia, the free encyclopedia
PPP1R14A
Identifiers
AliasesPPP1R14A, CPI-17, CPI17, PPP1INL, protein phosphatase 1 regulatory inhibitor subunit 14A
External IDsOMIM: 608153; MGI: 1931139; HomoloGene: 12267; GeneCards: PPP1R14A; OMA:PPP1R14A - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_033256
NM_001243947

NM_026731

RefSeq (protein)

NP_001230876
NP_150281

NP_081007

Location (UCSC)n/aChr 7: 28.99 – 28.99 Mb
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

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.[4][5][6]

Function

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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.

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

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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]

References

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  1. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037166Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ Eto M, Ohmori T, Suzuki M, Furuya K, Morita F (December 1995). "A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization". Journal of Biochemistry. 118 (6): 1104–1107. doi:10.1093/oxfordjournals.jbchem.a124993. PMID 8720121.
  5. ^ 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. PMID 11467857.
  6. ^ a b "Entrez Gene: PPP1R14A protein phosphatase 1, regulatory (inhibitor) subunit 14A".
  7. ^ Eto M (December 2009). "Regulation of cellular protein phosphatase-1 (PP1) by phosphorylation of the CPI-17 family, C-kinase-activated PP1 inhibitors". The Journal of Biological Chemistry. 284 (51): 35273–35277. doi:10.1074/jbc.R109.059972. PMC 2790955. PMID 19846560.
  8. ^ Tian Y, Soupir A, Liu Q, Wu L, Huang CC, Park JY, Wang L (November 2021). "Novel role of prostate cancer risk variant rs7247241 on PPP1R14A isoform transition through allelic TF binding and CpG methylation". Human Molecular Genetics. 31 (10): 1610–1621. doi:10.1093/hmg/ddab347. PMC 9122641. PMID 34849858.

Further reading

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