Physical and functional interactions of Galphaq with Rho and its exchange factors.
Recent reports have shown that several heterotrimeric protein-coupled receptors that signal through Galpha(q) can induce Rho-dependent responses, but the pathways that mediate the interaction between Galpha(q) and Rho have not yet been identified. In this report we present evidence that Galpha(q) expressed in COS-7 cells coprecipitates with the Rho guanine nucleotide exchange factor (GEF) Lbc. Furthermore, Galpha(q) expression enhances Rho-dependent responses. Coexpressed Galpha(q) and Lbc have a synergistic effect on the Rho-dependent rounding of 1321N1 astrocytoma cells. In addition, serum response factor-dependent gene expression, as assessed by the SRE.L reporter gene, is synergistically activated by Galpha(q) and Rho GEFs. The synergistic effect of Galpha(q) on this response is inhibited by C3 exoenzyme and requires phospholipase C activation. Surprisingly, expression of Galpha(q), in contrast to that of Galpha(12) and Galpha(13), does not increase the amount of activated Rho. We also observe that Galpha(q) enhances SRE.L stimulation by activated Rho, indicating that the effect of Galpha(q) occurs downstream of Rho activation. Thus, Galpha(q) interacts physically and/or functionally with Rho GEFs; however this does not appear to lead to or result from increased activation of Rho. We suggest that Galpha(q)-generated signals enhance responses downstream of Rho activation.
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0636, USA.
S A
SA
Sagi
T M
TM
Seasholtz
M
M
Kobiashvili
B A
BA
Wilson
D
D
Toksoz
J H
JH
Brown
D000818:Animals; D019556:COS Cells; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D014158:Transcription, Genetic; D010738:Type C Phospholipases / Q000378:metabolism
D020662:Guanine Nucleotide Exchange Factors; D011493:Protein Kinase C; D010738:Type C Phospholipases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins