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Role of transglutaminase II in retinoic acid‐induced activation of RhoA‐associated kinase‐2
Author(s) -
Singh Ugra S.,
Kunar Matthew T.,
Kao YuLin,
Baker Kenneth M.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.10.2413
Subject(s) - library science , medicine , research center , rhoa , gerontology , chemistry , pathology , signal transduction , biochemistry , computer science
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.