Role of transglutaminase II in retinoic acid-induced activation of RhoA-associated kinase-2.
Transamidation is a post-translational modification of proteins mediated by tissue transglutaminase II (TGase), a GTP-binding protein, participating in signal transduction pathways as a non-conventional G-protein. Retinoic acid (RA), which is known to have a role in cell differentiation, is a potent activator of TGASE: The activation of TGase results in increased transamidation of RhoA, which is inhibited by monodansylcadaverine (MDC; an inhibitor of transglutaminase activity) and TGaseM (a TGase mutant lacking transglutaminase activity). Transamidated RhoA functions as a constitutively active G-protein, showing increased binding to its downstream target, RhoA-associated kinase-2 (ROCK-2). Upon binding to RhoA, ROCK-2 becomes autophosphorylated and demonstrates stimulated kinase activity. The RA-stimulated interaction between RhoA and ROCK-2 is blocked by MDC and TGaseM, indicating a role for transglutaminase activity in the interaction. Biochemical effects of TGase activation, coupled with the formation of stress fibers and focal adhesion complexes, are proposed to have a significant role in cell differentiation.
Singh
U S
US
Division of Molecular Cardiology, Cardiovascular Research Institute, The Texas A&M University System Health Science Center, College of Medicine, 1901 South 1st Street, Temple, TX 76504, USA. Usingh@medicine.tamu.edu
Kunar
M T
MT
Kao
Y L
YL
Baker
K M
KM
D003599:Cytoskeleton / Q000502:physiology; D004789:Enzyme Activation; D022001:Focal Adhesions; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011503:Transglutaminases / Q000378:metabolism / Q000502:physiology*; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D014212:Tretinoin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein