CDC25(Mm)/Ras-GRF1 regulates both Ras and Rac signaling pathways

The Ras-GRF1 exchange factor molecule contains in addition to the catalytic domain two pleckstrin homology (PH1 and PH2), one IQ and one Dbl homology (DH) domains, In this study ne investigated the role of such additional dom ains. We found that a Ras-GRF1 mutant lacking PH1 and IQ domains is suffici ent to activate c-fos promoter in response to lysophosphatidic acid (LPA). The same mutant did not increase external stimuli-regulated kinase (ERK) ac tivity, suggesting an additional mechanism for the induction of gene transc ription. Isolated DHPH2 module activates c-Jun NH2-terminal kinase and the c-fos promoter in response to LPB, providing the basis for an ERK-independe nt mechanism. These results provide evidence that Ras-GRF1 acts as a bifunc tional molecule on both ERK-dependent and independent pathways. (C) 1999 Fe deration of European Biochemical Societies.