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			PubMed Journals: Mol Cell Biol

  Source:		PMID: 14966296


    		Mol Cell Biol. 2004 Mar;24(5):2190-201.
     
			Site-selective regulation of platelet-derived
			growth factor beta receptor tyrosine phosphorylation
			by T-cell protein tyrosine phosphatase.

			Persson C(1), Sävenhed C, Bourdeau A, Tremblay
			ML, Markova B, Böhmer FD, Haj FG, Neel BG,
			Elson A, Heldin CH, Rönnstrand L, Ostman
			A, Hellberg C.

			Author Information
			(1) Ludwig Institute for Cancer Research,
			Uppsala Branch, Biomedical Center, S-751
			24 Uppsala, Sweden.

			The platelet-derived growth factor (PDGF)
			beta receptor mediates mitogenic and chemotactic
			signals. Like other tyrosine kinase receptors,
			the PDGF beta receptor is negatively regulated
			by protein tyrosine phosphatases (PTPs).
			To explore whether T-cell PTP (TC-PTP) negatively
			regulates the PDGF beta receptor, we compared
			PDGF beta receptor tyrosine phosphorylation
			in wild-type and TC-PTP knockout (ko) mouse
			embryos. PDGF beta receptors were
			hyperphosphorylated in TC-PTP ko embryos.
			Fivefold-higher ligand-induced receptor
			phosphorylation was observed in TC-PTP ko
			mouse embryo fibroblasts (MEFs) as well.
			Reexpression of TC-PTP partly abolished
			this difference. As determined with site-specific
			phosphotyrosine antibodies, the extent of
			hyperphosphorylation varied among different
			autophosphorylation sites. The phospholipase
			Cgamma1 binding site Y1021, previously implicated
			in chemotaxis, displayed the largest increase
			in phosphorylation. The increase in Y1021
			phosphorylation was accompanied by increased
			phospholipase Cgamma1 activity and migratory
			hyperresponsiveness to PDGF. PDGF beta receptor
			tyrosine phosphorylation in PTP-1B ko MEFs
			but not in PTPepsilon ko MEFs was also higher
			than that in control cells. This increase
			occurred with a site distribution different
			from that seen after TC-PTP depletion. PDGF-induced
			migration was not increased in PTP-1B ko
			cells. In summary, our findings identify
			TC-PTP as a previously unrecognized negative
			regulator of PDGF beta receptor signaling
			and support the general notion that PTPs
			display site selectivity in their action
			on tyrosine kinase receptors.

			PMCID: PMC350555 PMID: 14966296 [Indexed
			for MEDLINE]

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