12/07/2007

Rho GTPase

Rho GTPases play central roles as molecular switches in diverse biological processes such as actin cytoskeleton organization, cell cycle regulation, cytoskeleton (cell morphology, cell polarity, cell movement, and alteration of gene expression, progression of cell cycle, chemotaxis, axonal guidance, malignant transformation, and epithelial wound repair.

Rho and its relatives, Rac and Cdc42, are members of a family of signaling proteins that act as molecular switches. Rho proteins are modulated between an active GTP-bound state and an inactive GDP-bound state, where state of activation controlled by regulatory proteins: guanine exchange factors (GEFs), which catalyze the exchange of GDP for GTP thereby activating Rho, guanine dissociation inhibitors (GDIs), which inhibit the release of GDP keeping Rho inactive, and GTPase activating proteins (GAPs), which increase the rate at which Rho hydrolyzes GTP and hence is inactivated.

Once activated, Rho GTPases interact with cellular target, effector proteins to drive axonal guidance, reorganization of the actin cytoskeleton (morphogenesis, cell polarity, cell movement, and cytokinesis), regulation of gene expression, chemotaxis, cell cycle progression, oncogenic transformation, and epithelial wound repair.

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