title: v-mos suppresses platelet-derived growth factor (PDGF) type-beta receptor autophosphorylation and inhibits PDGF-BB-mediated signal transduction.
abstract: The function of mos protein in somatic cells, the mechanisms underlying its ability to transform cells, and its relationship to growth factor autonomy and growth factor-mediated signal transduction are not well defined. This report demonstrates that the expression of transforming mos (v-mos) can block the stimulation of growth-related gene expression mediated by the platelet-derived growth factor (PDGF-BB). This blockade by v-mos of PDGF-BB signal transduction occurs very early in the signalling pathway, at the level of PDGF type-beta receptor autophosphorylation. Although the expression of PDGF type-beta receptor, as detected by Western blot with anti-PDGF type-beta receptor antibody,was not diminished in v-mos transformed BALB/c-3T3 murine fibroblasts, the autophosphorylation of PDGF-beta receptor in response to ligand (recombinant PDGF-BB homodimer) stimulation was profoundly suppressed. This same phenomenon of v-mos-mediated PDGF type-beta receptor autophosphorylation inhibition was also demonstrated in NIH-3T3 fibroblasts. A v-mos mutant gene, which was incapable of binding ATP and was kinase-defective, did not block ligand-mediated receptor autophosphorylation. Factor(s) present in v-mos expressing fibroblasts, and found in the membrane fractions of these cells, dominantly inhibit the autophosphorylation of the PDGF type-beta receptor obtained from normal fibroblasts. This trans-acting factor does not appear to be a protein-tyrosine phosphatase. These findings suggest a role for mos, or a similar serine/threonine kinase, as a control mechanism in one of the earliest steps of the PDGF signal transduction pathway, and may provide a model for the functional interaction of mos with growth factor receptors.
authors.affiliation: Cancer Research Center, Boston University School of Medicine, Massachusetts 02118.
authors.forename: D V
authors.initials: DV
authors.lastname: Faller
authors.forename: L J
authors.initials: LJ
authors.lastname: Mundschau
authors.forename: L W
authors.initials: LW
authors.lastname: Forman
authors.forename: M A
authors.initials: MA
authors.lastname: Quiñones
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000077214:Becaplermin; D002461:Cell Line, Transformed; D002846:Chromatography, Affinity; D015870:Gene Expression; D017781:Genes, Immediate-Early; D016258:Genes, mos; D016259:Genes, myc; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017232:Oncogene Proteins v-mos / Q000096:biosynthesis*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D017479:Receptors, Platelet-Derived Growth Factor / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
chemical_list: D017232:Oncogene Proteins v-mos; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor