Protein kinase-c activation inhibits tyrosine phosphorylation of the c-met protein

Lucia Gandino, M. Flavia Di Renzo, Silvia Giordano, Federico Bussolino, Paolo M. Comoglio

Research output: Contribution to journalArticlepeer-review

Abstract

The mature product of the c-met proto-oncogene is a putative tyrosine kinase receptor of 190 kd with an αβ heterodimeric structure. The c-met protein is phosphorylated in vivo on the β subunit in the gastric carcinoma cell line GTL-16 (Giordano et al., 1988). Western blots with phosphotyrosine antibodies show that tyrosine phosphorylation of the β subunit is reduced by treatment of GTL-16 cells with protein kinase C activators (tumor promoting phorbol esters such as phorbol 12-myristate 13-acetate, TPA, and β-phorbol 12,13-dibutyrate, PdBu, or membrane permeable synthetic diacylglycerol 1-oleyl-2-acetyl-sn-glycerol, OAG). The inactive analog α-phorbol 12,13-didecanoate has no effect. The inhibition induced by TPA is dose dependent and maximal after 1 h. Depletion of protein kinase-C by prolonged treatment with TPA (18-48 h) increases the phosphorylation on tyrosine of the β subunit. Phospho-amino acid analysis of the c-met protein immunoprecipitated from [32P]orthophosphate-labelled GTL-16 cells shows that protein kinase-C activation leads to an increase in serine phosphorylation and to concomitant decrease in tyrosine phosphorylation. These results suggest that, similar to the EGF and insulin receptor, the putative receptor encoded by the c-met proto-oncogene may be negatively modulated by protein kinase-C phosphorylation.

Original languageEnglish
Pages (from-to)721-725
Number of pages5
JournalOncogene
Volume5
Issue number5
Publication statusPublished - May 1990

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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