Jh. Mao et al., GUANINE-NUCLEOTIDE EXCHANGE FACTOR GEF115 SPECIFICALLY MEDIATES ACTIVATION OF RHO AND SERUM RESPONSE FACTOR BY THE G-PROTEIN ALPHA-SUBUNIT G-ALPHA-13, Proceedings of the National Academy of Sciences of the United Statesof America, 95(22), 1998, pp. 12973-12976
Signal transduction pathways that mediate activation of serum response
factor (SRF) by heterotrimeric G protein Lu subunits were characteriz
ed in transfection systems. G alpha q, G alpha 12, and Ga13, but not G
alpha i, activate SRF through RhoA. When G alpha q, alpha 12, or alph
a 13 were coexpressed with a Rho-specific guanine nucleotide exchange
factor GEF115, G alpha 13, but not G alpha q or G alpha 12, showed syn
ergistic activation of SRF with GEF115. The synergy between G alpha 13
and GEF115 depends on the N-terminal part of GEF11S, and there was no
synergistic effect between G alpha 13 and another Rho-specific exchan
ge factor Lbc, In addition, the Dbl-homology (DH)-domain-deletion muta
nt of GEF115 inhibited G alpha 13- and G alpha 12-induced, but not GEF
115 itself- or G alpha q-induced, SRF activation. The DH-domain-deleti
on mutant also suppressed thrombin and lysophosphatidic acid-induced S
RF activation in NIH 3T3 cells, probably by inhibition of G alpha 12/1
3. The N-terminal part of GEF115 contains a sequence motif that is hom
ologous to the regulator of G protein signaling (RGS) domain of RGS12.
RGS12 can inhibit both G alpha 12 and G alpha 13, Thus, the inhibitio
n of Gcu12/13 by the DH deletion mutant may be due to the RGS activity
of the mutant, The synergism between G alpha 13 and GEF115 indicates
that GEF115 mediates G alpha 13-induced activation of Rho and SRF.