Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding site, abrogates signal transduction by the murine CSF-1 receptor expressed in Rat-2 fibroblasts.

摘要: The receptor for the myeloid cell growth factor colony stimulating 1 (CSF-1) is a protein tyrosine kinase that closely related to PDGF receptor. Ligand binding results in activation and autophosphorylation. Three autophosphorylation sites, Tyr697, Tyr706 Tyr721, have been mapped insert domain. Deletion of entire domain completely abrogates signal transduction by CSF-1 expressed Rat-2 fibroblasts. To investigate function individual phosphorylation sites present domain, number site mutants were Mutation either Tyr697 or Tyr721 compromised A mutant receptor, which both replaced phenylalanine, has lost all ability induce changes morphology increase rate response CSF-1. identified recently as PI 3-kinase. Here we report GRB2 associates with upon ligand binding. on SHC several other GRB2-associated proteins increased stimulation was GRB2. We suggest 3-kinase, some could play an important role