Cell type-specific signaling function of RhoA GTPase: lessons from mouse gene targeting

RhoA GTPase is a key intracellular regulator of actomyosin dynamics and other cell functions, including adhesion, proliferation, survival, and gene expression. Most of our knowledge of RhoA signaling function is from studies in immortalized cell lines utilizing inhibitors or dominant mutant overexpression, both of which are limited in terms of specificity, dosage, and clonal variation. Recent mouse gene targeting studies of rhoA and its regulators/effectors have revealed cell type-specific signaling mechanisms in the context of mammalian physiology. The new knowledge may present therapeutic opportunities for the rational targeting of RhoA signaling-mediated pathophysiologies.