BROADLY EXPRESSED SNT-LIKE PROTEINS LINK FGF RECEPTOR STIMULATION TO ACTIVATORS OF RAS

SNT was originally described as a similar to 90 kilodalton protein in neuronal precursor cells which bears affinity for the yeast cell cycle protein p13(sucl) and which undergoes rapid tyrosine phosphorylation following stimulation with growth factors which trigger terminal diffe rentiation, but not by other growth factors which promote proliferatio n (Rabin et al,, 1993), We show here that similarly sized SNT-like pro teins (SLPs) are expressed in fibroblast, myoblast, and lymphoid cell lines, and undergo robust tyrosine phosphorylation in response to seve ral mitogenic ligands, including fibroblast growth factors (FGFs). SLP s are tyrosine phosphorylated within 15 s of FGF stimulation, are pred ominantly membrane-associated, and are weakly associated with activate d FGF receptor-1, suggesting that these proteins may be direct targets of the receptor kinase, Kinetic analysis of SLP phosphorylation and s tudies with serine/threonine kinase and phosphatase inhibitors suggest that SLPs are no larger than 70 000 kilodaltons, and that serine/thre onine phosphorylation follows tyrosine phosphorylation to substantiall y retard gel electrophoretic mobility, SLPs are associated with the Gr b-2 adaptor and are the major tyrosine phosphorylated proteins associa ted with the Ras guanine nucleotide exchange factor Sos in FGF-stimula ted fibroblasts, suggesting that SLP-Grb2-Sos complexes modulate the a ctivity of Ras proteins.