Rho-GTPases in Embryonic Stem Cells

摘要: The Rho family of small GTP-binding proteins is comprised 22 members, including the most well characterized members RhoA, Rac1 and Cdc42 (Jaffe Hall 2005). share a high degree homology with Ras proto-oncogene, indeed were first identified as result this similarity (Ras homologue). Activity these dependent upon their nucleotide binding state; inactive when associated GDP but active following exchange for GTP, which induces conformational changes that promote association/activation downstream effector proteins. GDP/GTP cycle regulated by GAPs accelerate GTP hydrolysis providing critical catalytic amino acid leading to return state (Bernards Settleman 2005), GEFs guanine consequent activation (Rossman et al. number far exceeds proteins, roles individual in specific cell types biological processes currently an intensively studied field. Although united function regulators actin cytoskeleton, each has distinct role organization structures (Figure 1). RhoA principally involved production actin-myosin bundles generation actomyosin contractile force. contributes formation meshworks emergence large protrusive lead spreading or, if occurring polarized manner, will contribute motility. promotes actin-rich filopodia. Together, coordinated programs activation/inactivation play prominent such endocytosis/exocytosis, adhesion motility, may subsequently impact proliferation death/survival. Recent advances development activation-state sensitive fluorescent probes have allowed temporal spatial analysis protein activation, added significantly our appreciation regulation (Hodgson 2010). Much early research on relied over-expression dominant-negative mutants reduced affinity constitutively-active hydrolysis; however, more refined become possible rise RNAi knockout methodologies (Heasman Ridley 2008). study historically focused molecular switches acting surface receptors regulate cytoskeleton Significant effort gone into classifying signaling from