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.
Mesh Terms:
Cytoskeleton, Enzyme Activation, Focal Adhesions, GTP-Binding Proteins, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Protein-Serine-Threonine Kinases, Transglutaminases, Tretinoin, rho-Associated Kinases, rhoA GTP-Binding Protein
Cytoskeleton, Enzyme Activation, Focal Adhesions, GTP-Binding Proteins, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Protein-Serine-Threonine Kinases, Transglutaminases, Tretinoin, rho-Associated Kinases, rhoA GTP-Binding Protein
EMBO J.
Date: May. 15, 2001
PubMed ID: 11350930
View in: Pubmed Google Scholar
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