v-mos suppresses platelet-derived growth factor (PDGF) type-beta receptor autophosphorylation and inhibits PDGF-BB-mediated signal transduction

• Published in: The Journal of biological chemistry 1994-02, Vol.269 (7), p.5022-5029
• Main Authors: FALLER, D. V, MUNDSCHAU, L. J, FORMAN, L. W, QUINONES, M. A
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Amino Acid Sequence; Animals; Becaplermin; Biological and medical sciences; Cell Line, Transformed; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromatography, Affinity; Fundamental and applied biological sciences. Psychology; Gene Expression; Genes, Immediate-Early; Genes, mos; Genes, myc; Mice; Mice, Inbred BALB C; Molecular and cellular biology; Molecular Sequence Data; Oncogene Proteins v-mos - biosynthesis; Phosphorylation; Platelet-Derived Growth Factor - metabolism; Platelet-Derived Growth Factor - pharmacology; Proto-Oncogene Proteins c-sis; Receptors, Platelet-Derived Growth Factor - isolation & purification; Receptors, Platelet-Derived Growth Factor - metabolism; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)37648-2

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.