Disruption of PDGF receptor trafficking by mutation of its PI-3 kinase binding sites.
Human platelet-derived growth factor receptors (PDGFRs) expressed in human Hep G2 cells internalized and concentrated in a juxtanuclear region near the Golgi network within 10 minutes after the cells were treated with PDGF. A PDGFR mutant (F5) that lacks high-affinity binding sites for the Src homology 2 domain-containing proteins phosphatidylinositol-3 kinase (PI-3 kinase), Ras guanosine triphosphatase activating protein, 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 concentrate intracellularly. A PDGFR mutant lacking only PI-3 kinase binding sites failed to concentrate intracellularly. Thus, PI-3 kinase binding sites appear both necessary and sufficient for the normal endocytic trafficking of the activated PDGFR.
Joly
M
M
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester 01605.
Kazlauskas
A
A
Fay
F S
FS
Corvera
S
S
D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D020690:GTPase-Activating Proteins; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases; D051966:Phospholipase C gamma; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017479:Receptors, Platelet-Derived Growth Factor; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma