Journal
FEBS LETTERS
Volume 578, Issue 1-2, Pages 73-79Publisher
WILEY
DOI: 10.1016/j.febslet.2004.10.072
Keywords
myosin phosphatase; Ca2+-sensitization; smooth muscle; CPI-17; Rho guanine nucleotide exchange factors
Funding
- NHLBI NIH HHS [P01 HL48807, P01 HL19242] Funding Source: Medline
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Ca2+-sensitization of smooth muscle occurs through inhibition of myosin light chain phosphatase (MLCP) leading to an increase in the MLCK:MLCP activity ratio. MLCP is inhibited through phosphorylation of its regulatory subunit (MYPT-1) following activation of the RhoA/Rho kinase (ROK) pathway or through phosphorylation of the PP1c inhibitory protein, CPI-17, by PKC delta or ROK. Here, we explore the crosstalk between these two modes of MLCP inhibition in a smooth muscle of a natural CPI-17 knockout, chicken amnion. GTPgammaS elicited Ca2+-sensitized force which was relaxed by GDI or Y-27632, however, U46619, carbachol and phorbol ester failed to induce Ca2+-sensitized force, but were rescued by recombinant CPI-17, and were sensitive to Y-27632 inhibition. In the presence, but not absence, of CPI-17, U46619 also significantly increased GTP RhoA. There was no affect on MYPT-1 phosphorylation at T695, however, T850 phosphorylation increased in response to GTPgammaS stimulation. Together, these data suggest a role for CPI-17 upstream of RhoA activation possibly through activation of another PP1 family member targeted by CPI-17. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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