Broadly expressed SNT-like proteins link FGF receptor stimulation to activators of Ras.
SNT was originally described as a approximately 90 kilodalton protein in neuronal precursor cells which bears affinity for the yeast cell cycle protein p13sucl and which undergoes rapid tyrosine phosphorylation following stimulation with growth factors which trigger terminal differentiation, but not by other growth factors which promote proliferation (Rabin et al., 1993). We show here that similarly sized SNT-like proteins (SLPs) are expressed in fibroblast, myoblast, and lymphoid cell lines, and undergo robust tyrosine phosphorylation in response to several mitogenic ligands, including fibroblast growth factors (FGFs). SLPs are tyrosine phosphorylated within 15 s of FGF stimulation, are predominantly membrane-associated, and are weakly associated with activated FGF receptor-1, suggesting that these proteins may be direct targets of the receptor kinase. Kinetic analysis of SLP phosphorylation and studies with serine/threonine kinase and phosphatase inhibitors suggest that SLPs are no larger than 70 000 kilodaltons, and that serine/threonine phosphorylation follows tyrosine phosphorylation to substantially retard gel electrophoretic mobility. SLPs are associated with the Grb-2 adaptor and are the major tyrosine phosphorylated proteins associated with the Ras guanine nucleotide exchange factor Sos in FGF-stimulated fibroblasts, suggesting that SLP-Grb2-Sos complexes modulate the activity of Ras proteins.
Wang
J K
JK
Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Xu
H
H
Li
H C
HC
Goldfarb
M
M
D016475:3T3 Cells; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D066246:ErbB Receptors / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D014443:Tyrosine / Q000378:metabolism
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D009419:Nerve Tissue Proteins; D017468:Receptors, Fibroblast Growth Factor; D029702:Schizosaccharomyces pombe Proteins; C051655:Suc1 protein, S pombe; D014443:Tyrosine; D066246:ErbB Receptors