Cell surface transglutaminase promotes RhoA activation via integrin clustering and suppression of the Src-p190RhoGAP signaling pathway.

ABSTRACT: Tissue transglutaminase (tTG) is a multifunctional protein that serves as cross-linking enzyme and integrin-binding adhesion coreceptor for fibronectin on the cell surface. Previous work showed activation of small GTPase RhoA via enzymatic transamidation by cytoplasmic tTG. Here, we report an alternative nonenzymatic mechanism of RhoA activation by cell surface tTG. Direct engagement of surface tTG with specific antibody or the fibronectin fragment containing modules I(6)II(1,2)I(7-9) increases RhoA-GTP levels. Integrin-dependent signaling to RhoA and its downstream target Rho-associated coiled-coil containing serine/threonine protein kinase (ROCK) is amplified by surface tTG. tTG expression on the cell surface elevates RhoA-GTP levels in nonadherent and adherent cells, delays maximal RhoA

SUBMITTER: Janiak A 

PROVIDER: S-EPMC1415321 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature