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 we investigated the role of such additional domains. We found that a Ras-GRF1 mutant lacking PH1 and IQ domains is sufficient to activate c-fos promoter in response to lysophosphatidic acid (LPA). The same mutant did not increase external stimuli-regulated kinase (ERK) activity, suggesting an additional mechanism for the induction of gene transcription. Isolated DH-PH2 module activates c-Jun NH2-terminal kinase and the c-fos promoter in response to LPA, providing the basis for an ERK-independent mechanism. These results provide evidence that Ras-GRF1 acts as a bifunctional molecule on both ERK-dependent and independent pathways.

Innocenti, M., Zippel, R., Brambilla, R., Sturani, E. (1999). CDC25(Mm)/Ras-GRF1 regulates both Ras and Rac signaling pathways. FEBS LETTERS, 460(2), 357-362 [10.1016/s0014-5793(99)01374-5].

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

Innocenti M;
1999

Abstract

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 we investigated the role of such additional domains. We found that a Ras-GRF1 mutant lacking PH1 and IQ domains is sufficient to activate c-fos promoter in response to lysophosphatidic acid (LPA). The same mutant did not increase external stimuli-regulated kinase (ERK) activity, suggesting an additional mechanism for the induction of gene transcription. Isolated DH-PH2 module activates c-Jun NH2-terminal kinase and the c-fos promoter in response to LPA, providing the basis for an ERK-independent mechanism. These results provide evidence that Ras-GRF1 acts as a bifunctional molecule on both ERK-dependent and independent pathways.
Articolo in rivista - Articolo scientifico
c-Jun NH2-terminal kinase; External stimuli-regulated kinase; Lysophosphatidic acid; Rac; Ras; Ras-GRF1;
English
1999
460
2
357
362
reserved
Innocenti, M., Zippel, R., Brambilla, R., Sturani, E. (1999). CDC25(Mm)/Ras-GRF1 regulates both Ras and Rac signaling pathways. FEBS LETTERS, 460(2), 357-362 [10.1016/s0014-5793(99)01374-5].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/396115
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