Interactions of phosphatidylinositol kinase, GTPase-activating protein (GAP), and GAP-associated proteins with the colony-stimulating factor 1 receptor.

摘要: The interactions of the macrophage colony-stimulating factor 1 (CSF-1) receptor with potential targets were investigated after ligand stimulation either mouse macrophages or fibroblasts that ectopically express CSF-1 receptors. In Rat-2 cells expressing receptor, full activation and cellular transformation require exogenous CSF-1, whereas NIH 3T3 c-fms are transformed by autocrine stimulation. Activated receptors physically associate a phosphatidylinositol (PI) 3'-kinase. A mutant deletion kinase insert region was deficient in its ability to bind functional PI 3'-kinase induce activity precipitable antiphosphotyrosine antibodies. fibroblasts, also induced phosphorylation GTPase-activating protein (GAP)-associated p62 on tyrosine, although GAP itself relatively poor substrate. contrast association, not markedly affected region. These results indicate selectively enhances CSF-1-dependent association active retains considerable transforming (G. Taylor, M. Reedijk, V. Rothwell, L. Rohrschneider, T. Pawson, EMBO J. 8:2029-2037, 1989). This more seriously impaired cell transformation, mutant-expressing still formed small colonies soft agar presence CSF-1. Therefore, through does result fibroblast transformation. interaction between may contribute play role CSF-1-stimulated macrophages.