IDENTIFICATION OF A NEW ADAPTER PROTEIN THAT MAY LINK THE COMMON BETA-SUBUNIT OF THE RECEPTOR FOR GRANULOCYTE MACROPHAGE COLONY-STIMULATINGFACTOR, INTERLEUKIN (IL)-3, AND IL-5 TO PHOSPHATIDYLINOSITOL 3-KINASE/

Binding of human granulocyte/macrophage colony-stimulating factor (hGM -CSF) to its receptor induces the rapid activation of phosphatidylinos itol-3 kinase (PI 3-kinase). As hGM-CSF receptor (hGMR) does not conta in a consensus sequence for binding of PI 3-kinase, hGMR must use a di stinct mechanism for its association with and activation of PI 3-kinas e. Here, we describe the identification of a tyrosine phosphorylated p rotein of 76-85 kDa (p80) that associates with the common beta subunit of hGMR and with the SH2 domains of the p85 subunit of PI 3-kinase in hGM-CSF stimulated cells. Src/Yes and Lyn were tightly associated wit h the p80 PI 3-kinase complex, suggesting that p80 and other phosphoty rosyl proteins present in the complex were phosphorylated by Src famil y kinases. Tyrosine phosphorylation of p80 was only detected in hGM-CS F or human interleukin-3-stimulated cells, suggesting that activation of p80 might be specific for signaling via the common beta subunit. We postulate that p80 functions as an adapter protein that may participa te in linking the hGM-CSF receptor to the PI 3-kinase signaling pathwa y.