To begin to understand how ras p21 might be coupled to the human colony stimulating factor-1 receptor (CSF-IR), we compared the signaling properties of a CSF-IR containing a point mutation that converts the tyrosine at position 809 to a phenylalanine residue to signal transduction in cells that co-express the wild-type receptor and the catalytic domain of the GTPase activating protein (GAP(C)). We find that modulation of the immediate early gene c-myc and a delayed early response represented by the retrotransposon NVL3 were selectively impaired in both situations. Further, constitutive expression of c-myc in cells that contain GAP(C) restored CSF-1-dependent signal transduction. The data suggest a model in which information important for mitogenic cell.growth flows from the region of the receptor containing tyrosine 809, through ras p21, to c-myc in the nucleus.

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