Activation of RhoA by association of Galpha(13) with Dbl.
RhoA is a small G protein that is implicated in the regulation of the actin cytoskeleton, gene expression, and cell cycle progression. It is activated by many agonists whose receptors are linked to heterotrimeric G proteins, but the mechanisms are incompletely understood. In this study, we show that the constitutively active alpha-subunit of the heterotrimeric G protein G(13) associated with the Rho family guanine nucleotide exchange factor Dbl in NIH 3T3 cells and that this resulted in activation of RhoA. This activation was not seen with wild-type Galpha(13) or if Dbl and active Galpha(13) were expressed separately and mixed. In contrast, coexpression of constitutively active Galpha(q) with Dbl did not lead to their association and caused a weak activation of RhoA that was no greater than that observed with wild-type Galpha(q). These findings illustrate that activated Galpha(13) and Dbl can associate in vivo and that this leads to Rho activation.
Jin
S
S
Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232-0295, USA.
Exton
J H
JH
D016475:3T3 Cells; D000818:Animals; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020662:Guanine Nucleotide Exchange Factors; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D051379:Mice; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D020662:Guanine Nucleotide Exchange Factors; C512843:Mcf2 protein, mouse; D015682:Retroviridae Proteins, Oncogenic; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein