Document 0475
 DOCN  M9480475
 TI    Oncostatin M activates phosphatidylinositol-3-kinase in Kaposi's sarcoma
       cells.
 DT    9410
 AU    Soldi R; Graziani A; Benelli R; Ghigo D; Bosia A; Albini A; Bussolino F;
       Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
 SO    Oncogene. 1994 Aug;9(8):2253-60. Unique Identifier : AIDSLINE
       MED/94309900
 AB    Oncostatin M (OM) is a polypeptide cytokine that induces autocrine and
       paracrine effects on AIDS-Kaposi's sarcoma (KS) cells (Nair et al.,
       Science, 255, 1430-1432, 1992; Miles et al., Science, 255, 1432-1434,
       1992). 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 phosphatidylinositol 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.
 DE    Antineoplastic Agents/*PHARMACOLOGY  Cytokines/*PHARMACOLOGY  Human
       Peptides/*PHARMACOLOGY  Phosphatidylinositols/METABOLISM
       Phosphorylation  Phosphotransferases (Alcohol Group
       Acceptor)/*METABOLISM  Protein-Tyrosine Kinase/METABOLISM  Sarcoma,
       Kaposi's/*ENZYMOLOGY  Support, Non-U.S. Gov't  Tumor Cells, Cultured
       Tyrosine/METABOLISM  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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