Abstract
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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites
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Cell Membrane / metabolism
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Endocytosis
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GTPase-Activating Proteins
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Golgi Apparatus / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins
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Isoenzymes / metabolism
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Mutation
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Phosphatidylinositol 3-Kinases
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Phospholipase C gamma
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Platelet-Derived Growth Factor / pharmacology
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / metabolism
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Proteins / metabolism
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Receptors, Platelet-Derived Growth Factor / genetics
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Receptors, Platelet-Derived Growth Factor / metabolism*
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Tumor Cells, Cultured
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Type C Phospholipases / metabolism
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ras GTPase-Activating Proteins
Substances
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GTPase-Activating Proteins
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Intracellular Signaling Peptides and Proteins
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Isoenzymes
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Platelet-Derived Growth Factor
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Proteins
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ras GTPase-Activating Proteins
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor)
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Receptors, Platelet-Derived Growth Factor
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PTPN11 protein, human
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PTPN6 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Type C Phospholipases
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Phospholipase C gamma