Prostate-apoptosis response-4 phosphorylation in vascular smooth muscle.

摘要: Abstract The protein prostate-apoptosis response (Par)-4 has been implicated in the regulation of smooth muscle contraction, based largely on studies with A7r5 cell line. A mechanism proposed whereby Par-4 binding to MYPT1 (the myosin-targeting subunit myosin light chain phosphatase, MLCP) blocks access zipper-interacting kinase (ZIPK) Thr697 and Thr855 MYPT1, whose phosphorylation is associated MLCP inhibition. Phosphorylation at Thr155 disrupts its interaction exposing sites leading inhibition contraction. We tested this “padlock” hypothesis a well-characterized vascular system, rat caudal artery. was retained Triton-skinned tissue, suggesting tight association contractile machinery, indeed co-immunoprecipitated MYPT1. Treatment tissue phosphatase inhibitor microcystin (MC) evoked Thr155, but did not induce dissociation from machinery. Furthermore, analysis time courses MC-induced revealed that or preceded phosphorylation. inhibited by non-selective staurosporine, inhibitors ZIPK, Rho-associated C. In addition, occur upon addition constitutively-active ZIPK skinned tissue. conclude does regulate contraction inducing allow MLCP.