DISRUPTION OF PDGF RECEPTOR TRAFFICKING BY MUTATION OF ITS PI-3 KINASE BINDING-SITES

Human platelet-derived growth factor receptors (PDGFRs) expressed in h uman Hep G2 cells internalized and concentrated in a juxtanuclear regi on near the Golgi network within 10 minutes after the cells were treat ed with PDGF. A PDGFR mutant (F5) that lacks high-affinity binding sit es for the Src homology 2 domain-containing proteins phosphatidylinosi tol-3 kinase (PI-3 kinase), Ras guanosine triphosphatase activating pr otein, phospholipase C-gamma, and a phosphotyrosine phosphatase (Syp) remained at the cell periphery. Restoration of the PI-3 kinase binding sites on F5 completely restored the ability of the receptor to concen trate intracellularly. A PDGFR mutant lacking only PI-3 kinase binding sites failed to concentrate intracellularly. Thus, PI-3 kinase bindin g sites appear both necessary and sufficient for the normal endocytic trafficking of the activated PDGFR.