Regulation of Ca2+-independent smooth muscle contraction by alternative staurosporine-sensitive kinase

It is well known that inhibition of myosin phosphatase induces smooth muscl e contraction in the absence of Ca2+. We characterized the kinase(s) which plays a role in Ca2+-independent, microcystin-LR-induced contraction in per meabilized smooth muscle of the rabbit portal vein. Assessments of various protein kinase inhibitors revealed this kinase(s) (1) was sensitive to stau rosporine (1 mu M), but resistant to other agents including wortmannin (10 mu M), Y-27632 ((R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecar boxamide, 100 mu M), HA1077 (1-(5-isoquinolinylsulfonyl)-homopiperazine, 10 0 mu M), H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, 100 mu M), an d calphostin C (100 mu M), and (2) induced phosphorylation of 20 kDa myosin light chain at serine-19. We concluded that other kinases exist which phos phorylate myosin light chain at serine-19 and induce Ca2+-independent smoot h muscle contraction, distinct from Rho-associated kinase, myosin light cha in kinase, and protein kinase C. (C) 1999 Elsevier Science B.V. All rights reserved.