Smooth muscle contraction by small GTPase Rho.
Abnormal contraction of vascular smooth muscle contributes to a variety of diseases such as hypertension and vasospasm in coronary and cerebral arteries. An increment in a cytoplasmic Ca2+ concentration is the key event in smooth muscle contraction. However, smooth muscle contraction is modified upon the stimulation by agonists as well as in some pathophysiological situations in Ca(2+)-independent mechanism. The molecular mechanism underlying this modulation was not elucidated. Recent studies have shown the important role of small GTPase Rho and its effector, Rho-associated kinase (Rho-kinase)/ROK/ROCK in Ca(2+)-independent regulation of smooth muscle contraction. The Rho/Rho-kinase pathway modulates the phosphorylation level of myosin light chain (MLC) of myosin II, mainly through the inhibition of myosin phosphatase, and contributes to the agonist-induced Ca(2+)-sensitization in smooth muscle contraction. The Rho/Rho-kinase pathway is involved in the pathogenesis of hypertension, vasospasm and arteriosclerosis, and is a potent target of new therapies for these diseases.
Kawano
Yoji
Y
Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Japan.
Yoshimura
Takeshi
T
Kaibuchi
Kozo
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D043263:Myosin-Light-Chain Phosphatase; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D010749:Phosphoprotein Phosphatases; D043263:Myosin-Light-Chain Phosphatase; D020741:rho GTP-Binding Proteins; D002118:Calcium