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PMID: 11350930 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Role of transglutaminase II in retinoic acid-induced activation of RhoA-associated kinase-2.

The EMBO journal ·Vol. 20 ·No. 10 ·2001-05-15 ·Pages 2413-23

Singh US, Kunar MT, Kao YL, Baker KM

Abstract

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/physiology Enzyme Activation Focal Adhesions GTP-Binding Proteins/metabolism,physiology HeLa Cells Humans Intracellular Signaling Peptides and Proteins Protein Glutamine gamma Glutamyltransferase 2 Protein Serine-Threonine Kinases/metabolism Transglutaminases/metabolism,physiology Tretinoin/metabolism,pharmacology rho-Associated Kinases rhoA GTP-Binding Protein/metabolism
Chemicals
Intracellular Signaling Peptides and Proteins Tretinoin Protein Glutamine gamma Glutamyltransferase 2 Transglutaminases Protein Serine-Threonine Kinases rho-Associated Kinases GTP-Binding Proteins rhoA GTP-Binding Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Singh U S
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. [email protected]
Kunar M T
Kao Y L
Baker K M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.10.2413
Email
[email protected]
Published
2001-05-15
Pages
2413-23
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125450
Subset
IM
Grants
PHS HHS · 58439 · United States
NHLBI NIH HHS · HL60529 · United States
External Links
PubMed source DOI: 10.1093/emboj/20.10.2413 PMC Full Text View journal details
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