Activation of the Ras-GRF/CDC25Mm exchange factor by lysophosphatidic acid.
The Ras-GRF exchange factor can activate Ras-dependent responses following the activation of heterotrimeric G-protein and calcium signalling. In stable lines of NIH-3T3 fibroblasts that express Ras-GRF, the agonist lysophosphatidic acid (LPA) increases the phosphorylation state and activity of Ras-GRF. The stimulation of Ras-GRF can be demonstrated in vitro, in an assay using recombinant Ras substrate, and in situ, by a selective increase in the ability of LPA to stimulate mitogen-activated protein (MAP) kinase. The increase in Ras-GRF phosphorylation state, which occurs on serine residues, and the increase in exchange factor activity are blocked by pretreatment with pertussis toxin. Activation of Ras-GRF by LPA can also be inhibited by chelation of intracellular calcium and treatment of the Ras-GRF with protein phosphatase 1 (PP1), supporting a model in which Ras-GRF serves to integrate signals from multiple transduction pathways.
Mattingly
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Department of Pharmacology, Wayne State University, Detroit, MI 48201, USA. r.mattingly@wayne.edu
Saini
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Macara
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D016475:3T3 Cells; D000818:Animals; D020013:Calcium Signaling; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D020666:ras-GRF1
D018797:Cell Cycle Proteins; D008246:Lysophospholipids; D020666:ras-GRF1