Conformational Activation of Radixin by G13 Protein α Subunit

Abstract

G 13 protein, one of the heterotrimeric guanine nucleotide-binding proteins (G proteins), regulates diverse and complex cellular responses by transducing signals from the cell surface presumably involving more than one pathway. Yeast two-hybrid screening of a mouse brain cDNA library identified radixin, a member of the ERM family of three closely related proteins (ezrin, radixin, and moesin), as a protein that interacted with G␣ 13 . Interaction between radixin and G␣ 13 was confirmed by in vitro binding assay and by co-immunoprecipitation technique. Activated G␣ 13 induced conformational activation of radixin, as determined by binding of radixin to polymerized F-actin and by immunofluorescence in intact cells. Finally, two dominant negative mutants of radixin inhibited G␣ 13 -induced focus formation of Rat-1 fibroblasts but did not affect Ras-induced focus formation. Our results identifying a new signaling pathway for G␣ 13 indicate that ERM proteins can be activated by and serve as effectors of heterotrimeric G proteins.

Cell fusion promotes chemoresistance in metastatic colon carcinoma

“…It has been reported that Ga13 directly interacts with radixin, a member of ERM proteins, and that this interaction results in a conformational activation of radixin. 34 This phenomenon is possibly due to competition between components of the Rho signaling pathway (for example, p115 Rho GEF) and radixin for Ga13 binding, (see Figure 8). Finally, these findings emphasize the role that ADAM10 and the cytoskeleton play in promoting metastatic cancer cell fusion.…”

N-terminal Short Sequences of α Subunits of the G12Family Determine Selective Coupling to Receptors

“…Recently, several proteins that interact with both G␣ 12 and G␣ 13 have been identified, including p115, a Rho guanine nucleotide exchange factor (10), cadherin (11), and radixin (12). Therefore, G␣ 12 and G␣ 13 are thought to transduce mutual downstream signaling through these effectors. In contrast, a variety of GPCRs appear to selectively couple to G␣ 12 or G␣ 13 (13).…”

“…Therefore, G␣ 12 and G␣ 13 are thought to transduce mutual downstream signaling through these effectors. In contrast, a variety of GPCRs appear to selectively couple to G␣ 12 or G␣ 13 (13). For example, thrombin and lysophosphatidic acid (LPA) have been shown to induce stress fiber formation via G␣ 12 and G␣ 13 , respectively, by using dominant negative mutants of G␣ 12 and G␣ 13 (13).…”

“…duce several biological responses via activation of Rho, a major downstream common target for G␣ 12 and G␣ 13 , including stimulation of stress fiber formation and focal adhesion assembly (3), induction of neurite retraction (4), induction of apoptosis (5), transformation of fibroblasts (6), activation of phospholipase D (7), inhibition of Ca 2ϩ -dependent exocytosis (8), and activation of c-Jun N-terminal kinase (9). Recently, several proteins that interact with both G␣ 12 and G␣ 13 have been identified, including p115, a Rho guanine nucleotide exchange factor (10), cadherin (11), and radixin (12).…”

Functional consequences of Gα13 mutations that disrupt interaction with p115RhoGEF

“…Several additional pathways might be involved in the a 13 -mediated regulation of cell growth and differentiation since a 13 , as previously demonstrated, is a very powerful transformant, whereas Rho is a weak one (Symons, 1996). Radixin, a member of the ERM family of proteins, and cadherins have also been linked to the transforming ability of a 13 (Vaiskunaite et al, 2000;Meigs et al, 2001Meigs et al, , 2002. Other proteins yet to be identified may also play a role.…”