Abstract
Oncostatin M (OM) is a polypeptide cytokine that induces autocrine and paracrine effects on AIDS-Kaposi's sarcoma (KS) cells. The signalling pathways underlying this activation are largely unknown. We have found that OM binding to KS cell lines in vitro identifies a higher affinity binding site (Kd 10-20 pM) with a lower affinity (Kd 1.5 nM), high capacity binding site. The binding of OM to its receptor at the KS cell surface stimulates a rapid tyrosine phosphorylation of multiple proteins, including the p85 regulatory subunit of phosphatidylinositol-3-kinase (PI3K). In addition OM can stimulate the in vivo activation of PI3K and increases the PI3K activity in anti-phosphotyrosine and anti-src kinase family antibody directed immunoprecipitates. Genistein, an inhibitor of tyrosine kinases, inhibits the synthesis of phosphatidylinistol 3,4-biphosphate and the growth of KS cells. Finally, OM enhances tyrosine kinase activity in immune complex kinase assay performed with antibody anti-src kinase family. These data suggest that in KS cells OM can stimulate formation of tyrosine kinase co-ordinate signalling complexes, containing at least src kinase family and PI3K, which can drive the accumulation of the putative second-messengers D3-phosphorylated phosphoinositides.
Original language | English |
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Pages (from-to) | 2253-2260 |
Number of pages | 8 |
Journal | Oncogene |
Volume | 9 |
Issue number | 8 |
Publication status | Published - Aug 1994 |
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics