RGD Reference Report - Phosphorylation of the myosin phosphatase inhibitors, CPI-17 and PHI-1, by integrin-linked kinase. - Rat Genome Database

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Phosphorylation of the myosin phosphatase inhibitors, CPI-17 and PHI-1, by integrin-linked kinase.

Authors: Deng, JT  Sutherland, C  Brautigan, DL  Eto, M  Walsh, MP 
Citation: Deng JT, etal., Biochem J 2002 Oct 15;367(Pt 2):517-24.
RGD ID: 633111
Pubmed: PMID:12144526   (View Abstract at PubMed)
PMCID: PMC1222907   (View Article at PubMed Central)
DOI: DOI:10.1042/BJ20020522   (Journal Full-text)

Integrin-linked kinase (ILK) has been implicated in Ca(2+)- independent contraction of smooth muscle via its ability to phosphorylate myosin. We investigated the possibility that this kinase might also phosphorylate and regulate the myosin light-chain phosphatase inhibitor proteins CPI-17 [protein kinase C (PKC)-dependent phosphatase inhibitor of 17 kDa] and PHI-1 (phosphatase holoenzyme inhibitor-1), known substrates of PKC. Both phosphatase inhibitors were phosphorylated by ILK in an in-gel kinase assay and in solution. A Thr-->Ala mutation at Thr(38) of CPI-17 and Thr(57) of PHI-1 eliminated phosphorylation by ILK. Phosphopeptide mapping, phospho amino acid analysis and immunoblotting using phospho-specific antibodies indicated that ILK predominantly phosphorylated the site critical for potent inhibition, i.e. Thr(38) of CPI-17 or Thr(57) of PHI-1. CPI-17 and PHI-1 thiophosphorylated by ILK at Thr(38) or Thr(57) respectively inhibited myosin light-chain phosphatase (MLCP) activity bound to myosin, whereas the site-specific mutants CPI-17-Thr(38)Ala and PHI-1-Thr(57)Ala, treated with ILK under identical conditions, like the untreated wild-type proteins had no effect on the phosphatase. Consistent with these effects, both thiophospho-CPI-17 and -PHI-1 induced Ca(2+) sensitization of contraction of Triton X-100-demembranated rat-tail arterial smooth muscle, whereas CPI-17-Thr(38)Ala and PHI-1-Thr(57)Ala treated with ILK in the presence of adenosine 5'-[gamma-thio]triphosphate failed to evoke a contractile response. We conclude that ILK may activate smooth-muscle contraction both directly, via phosphorylation of myosin, and indirectly, via phosphorylation and activation of CPI-17 and PHI-1, leading to inhibition of MLCP.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
phosphatase inhibitor activity  IDA 633111 RGD 
protein phosphatase regulator activity  IDA 633111 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppp1r14b  (protein phosphatase 1, regulatory (inhibitor) subunit 14B)

Objects referenced in this article
Gene Ilk integrin-linked kinase Rattus norvegicus
Gene Ppp1r14a protein phosphatase 1, regulatory (inhibitor) subunit 14A Rattus norvegicus

Additional Information