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Platelet-derivedGrowth FactorReceptor-β (PDGFR-β)Activation PromotesIts Association withthe Low DensityLipoproteinReceptor-relatedProtein (LRP) Christopher NewtonElena LoukinovaIrina Mikhailenko2005 год

Platelet-derived Growth Factor Receptor-β (PDGFR-β) Activation Promotes Its Association with the Low Density Lipoprotein Receptor-related Protein (LRP)
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Аннотация: Activation of the platelet-derived growth factor receptor-beta (PDGFR-beta) leads to tyrosine phosphorylation of the cytoplasmic domain of LRP and alters its association with adaptor and signaling proteins, such as Shc. The mechanism of the PDGF-induced LRP tyrosine phosphorylation is not well understood, especially since PDGF not only activates PDGF receptor but also binds directly to LRP. To gain insight into this mechanism, we used a chimeric receptor in which the ligand binding domain of the PDGFR-beta was replaced with that from the macrophage colony-stimulating factor (M-CSF) receptor, a highly related receptor tyrosine kinase of the same subfamily, but with different ligand specificity. Activation of the chimeric receptor upon the addition of M-CSF readily mediated the tyrosine phosphorylation of LRP. Since M-CSF is not recognized by LRP, these results indicated that growth factor binding to LRP is not necessary for this phosphorylation event. Using a panel of cytoplasmic domain mutants of the chimeric M-CSF/PDGFR-beta, we confirmed that the kinase domain of PDGFR-beta is absolutely required for LRP tyrosine phosphorylation but that PDGFR-beta-mediated activation of phosphatidylinositol 3-kinase, RasGAP, SHP-2, phospholipase C-gamma, and Src are not necessary for LRP tyrosine phosphorylation. To identify the cellular compartment where LRP and the PDGFR-beta may interact, we employed immunofluorescence and immunogold electron microscopy. In WI-38 fibroblasts, these two receptors co-localized in coated pits and endosomal compartments following PDGF stimulation. Further, phosphorylated forms of the PDGFR-beta co-immunoprecipitated with LRP following PDGF treatment. Together, these studies revealed close association between activated PDGFR-beta and LRP, suggesting that LRP functions as a co-receptor capable of modulating the signal transduction pathways initiated by the PDGF receptor from endosomes.
Год издания: 2005
Авторы: Christopher Newton, Elena Loukinova, Irina Mikhailenko, Sripriya Ranganathan, Yamei Gao, Christian C. Haudenschild, Dudley K. Strickland
Издательство: Elsevier BV
Источник: Journal of Biological Chemistry
Ключевые слова: Caveolin-1 and cellular processes, Cell Adhesion Molecules Research, Protease and Inhibitor Mechanisms
Другие ссылки: Journal of Biological Chemistry (PDF)
Journal of Biological Chemistry (HTML)
PubMed (HTML)