Girish Mahajan (Editor)

PPP1R14A

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Species
  
Human

Entrez
  
94274

Human
  
Mouse

Ensembl
  
ENSG00000167641

Aliases
  
PPP1R14A, CPI-17, CPI17, PPP1INL, protein phosphatase 1 regulatory inhibitor subunit 14A

External IDs
  
MGI: 1931139 HomoloGene: 12267 GeneCards: PPP1R14A

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.

Contents

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.

    References

    PPP1R14A Wikipedia