PPP1R14A

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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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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 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