Regulation of Ca2+-independent smooth muscle contraction by alternative staurosporine-sensitive kinase.
It is well known that inhibition of myosin phosphatase induces smooth muscle contraction in the absence of Ca2+. We characterized the kinase(s) which plays a role in Ca2+-independent, microcystin-LR-induced contraction in permeabilized smooth muscle of the rabbit portal vein. Assessments of various protein kinase inhibitors revealed this kinase(s) (1) was sensitive to staurosporine (1 microM), but resistant to other agents including wortmannin (10 microM), Y-27632 ((R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide+ ++, 100 microM). HA1077 (1-(5-isoquinolinylsulfonyl)-homopiperazine, 100 microM), H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, 100 microM), and calphostin C (100 microM), and (2) induced phosphorylation of 20 kDa myosin light chain at serine-19. We concluded that other kinases exist which phosphorylate myosin light chain at serine-19 and induce Ca2+-independent smooth muscle contraction, distinct from Rho-associated kinase, myosin light chain kinase, and protein kinase C.
Kureishi
Y
Y
First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
Ito
M
M
Feng
J
J
Okinaka
T
T
Isaka
N
N
Nakano
T
T
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D052998:Microcystins; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009219:Myosin-Light-Chain Kinase / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D012234:Rho Factor / Q000187:drug effects* / Q000378:metabolism; D019311:Staurosporine / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000577:Amides; D004791:Enzyme Inhibitors; D052998:Microcystins; D010456:Peptides, Cyclic; D011725:Pyridines; D012234:Rho Factor; D014662:Vasoconstrictor Agents; C108830:Y 27632; C078588:microcystin; D009219:Myosin-Light-Chain Kinase; D019311:Staurosporine