Inhibition of ROCK by RhoE.
RhoE belongs to the Rnd subfamily of small Rho-related GTP-binding proteins. Similar to other Rho proteins, RhoE regulates actin cytoskeleton dynamics. Expression of RhoE induces loss of actin stress fibers, and it also increases cell migration speed. In part, this is due to RhoE interaction with the RhoA effector ROCK I, a serine/threonine kinase that regulates the formation and contractility of stress fibers. Interestingly, RhoE does not interact with the highly homologous kinase ROCK II. RhoE binding inhibits ROCK I from phosphorylating its downstream target myosin light chain phosphatase, thus increasing the activity of the phosphatase to dephosphorylate myosin II, which results in reduced actomyosin contractility. RhoE itself is phosphorylated by ROCK I, and this may enhance RhoE regulation of ROCK I function. This chapter describes the method used for studying ROCK inhibition by RhoE.
Ludwig Institute for Cancer Research, University College London, UK.
Kirsi
K
Riento
Anne J
AJ
Ridley
D000818:Animals; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology*; D005982:Glutathione Transferase / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D041701:Swiss 3T3 Cells; D020741:rho GTP-Binding Proteins; D054460:rho-Associated Kinases
D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; C085379:rho GTPase-activating protein; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; C513341:Rnd3 protein, mouse; D020741:rho GTP-Binding Proteins