El-Toukhy Amr, Given Allison M, Ogut Ozgur, Brozovich Frank V
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
FEBS Lett. 2006 Oct 16;580(24):5779-84. doi: 10.1016/j.febslet.2006.09.035. Epub 2006 Sep 27.
In avian smooth muscles, GTPgammaS produces a Rho kinase mediated increase in PHI-1 phosphorylation and force, but whether this correlation is causal is unknown. We examined the effect of phosphorylated PHI-1 (P-PHI-1) on force and myosin light chain (MLC(20)) phosphorylation at a constant [Ca(2+)]. P-PHI-1, but not PHI-1, increased MLC(20) phosphorylation and force, and phosphorylation of PHI-1 increased the interaction of PHI-1 with PP1c. Microcystin induced a dose-dependent reduction in the binding of PHI-1 to PP1c. These results suggest PHI-1 inhibits myosin light chain phosphatase by interacting with the active site of PP1c to produce a Ca(2+) independent increase in MLC(20) phosphorylation and force.
在禽类平滑肌中，GTPγS可使Rho激酶介导的PHI-1磷酸化及张力增加，但这种相关性是否存在因果关系尚不清楚。我们在恒定[Ca²⁺]条件下研究了磷酸化的PHI-1（P-PHI-1）对张力及肌球蛋白轻链（MLC₂₀）磷酸化的影响。P-PHI-1而非PHI-1可增加MLC₂₀磷酸化及张力，且PHI-1的磷酸化增加了PHI-1与PP1c的相互作用。微囊藻毒素可使PHI-1与PP1c的结合呈剂量依赖性减少。这些结果表明，PHI-1通过与PP1c的活性位点相互作用抑制肌球蛋白轻链磷酸酶，从而在不依赖Ca²⁺的情况下使MLC₂₀磷酸化及张力增加。
