title: Insulin-induced dissociation of Sos from Grb2 does not contribute to the down regulation of Ras activation.
abstract: Activation of Ras by a number of receptor tyrosine kinases is mediated by the guanine nucleotide exchange factor Sos. This activation is thought to occur as a result of the recruitment to the plasma membrane of a complex consisting of Sos and the adaptor molecule Grb2. Growth factor stimulation has been shown to induce the rapid phosphorylation of Sos on serine and threonine residues. In rat L6 cells, insulin-induced Sos phosphorylation is accompanied by a partial dissociation of the Grb2-Sos complex. In this study we have investigated the relationship between Sos phosphorylation and Grb2 association. To this end, we have utilized cAMP because it has been demonstrated that elevation of cytoplasmic levels of cAMP inhibits growth factor-induced Sos phosphorylation. We show that in rat L6 cells, cAMP treatment prevents both the insulin-stimulated Sos phosphorylation and Grb2 dissociation. However, cAMP treatment has no effect on the duration of insulin-induced Ras activation. These results suggest that the kinetics of Ras activation are independent of the phosphorylation-induced dissociation of Sos from Grb2.
authors.affiliation: Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, 11794-8621, USA.
authors.forename: S
authors.initials: S
authors.lastname: Corbalan-Garcia
authors.forename: K R
authors.initials: KR
authors.lastname: Degenhardt
authors.forename: D
authors.initials: D
authors.lastname: Bar-Sagi
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology*; D015536:Down-Regulation; D051380:GRB2 Adaptor Protein; D005786:Gene Expression Regulation / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects*; D020662:Guanine Nucleotide Exchange Factors; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D020663:ras Guanine Nucleotide Exchange Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495950:Grb2 protein, rat; D020662:Guanine Nucleotide Exchange Factors; D007328:Insulin; D011506:Proteins; D020663:ras Guanine Nucleotide Exchange Factors; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases