[Cellular functions & pharmacological manipulations of the small GTPase Rho & Rho effectors].
Rho is a member of the Ras-related family of small molecular weight GTP-binding proteins, and works as a molecular switch by shuttling between the GDP-bound inactive form and the GTP-bound active form. Cellular functions of Rho have been studied by two ways; one is to express or microinject constitutively active Rho mutants in cells to identify the active phenotype of Rho, and the other is to use botulinum C3 exoenzyme that specifically ADP-ribosylates and inactivates Rho in cells to find out phenotypes of Rho inactivation. These analyses have revealed that Rho is involved in cell to substratum adhesion and motility, cell contraction and cytokinesis through the reorganization of the actincytoskeleton and modulation of its activity. These actions of Rho are mediated by downstream Rho effectors. Several putative Rho effectors have been isolated on the basis of their selective binding to the GTP-bound form of Rho. Among them, the ROCK family of Rho-associated serine/threonine protein kinases inactivates cofilin and myosin phosphatase to induce stabilization of filamentous actin and increase in the actomyosin-based contractility. mDia binds profilin likely to promote actin polymerization. Thus, these effectors in combination are supposed to work in organization of various forms of the actin cytoskeleton. Furthermore, analyses using a ROCK specific inhibitor Y-27632 have suggested that the Rho-ROCK pathway works in contractions of vascular and bronchial smooth muscles under various pathological conditions and is involved in malignant cell transformation and tumor invasion and metastasis.
Narumiya
S
S
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins