Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase.
(2004) In Molecular and Cellular Biology 24(5). p.201-2190- Abstract
- The platelet-derived growth factor (PDGF) ß receptor mediates mitogenic and chemotactic signals. Like other tyrosine kinase receptors, the PDGF ß receptor is negatively regulated by protein tyrosine phosphatases (PTPs). To explore whether T-cell PTP (TC-PTP) negatively regulates the PDGF ß receptor, we compared PDGF ß receptor tyrosine phosphorylation in wild-type and TC-PTP knockout (ko) mouse embryos. PDGF ß 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... (More)
- The platelet-derived growth factor (PDGF) ß receptor mediates mitogenic and chemotactic signals. Like other tyrosine kinase receptors, the PDGF ß receptor is negatively regulated by protein tyrosine phosphatases (PTPs). To explore whether T-cell PTP (TC-PTP) negatively regulates the PDGF ß receptor, we compared PDGF ß receptor tyrosine phosphorylation in wild-type and TC-PTP knockout (ko) mouse embryos. PDGF ß 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 C1 binding site Y1021, previously implicated in chemotaxis, displayed the largest increase in phosphorylation. The increase in Y1021 phosphorylation was accompanied by increased phospholipase C1 activity and migratory hyperresponsiveness to PDGF. PDGF ß receptor tyrosine phosphorylation in PTP-1B ko MEFs but not in PTP 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 ß receptor signaling and support the general notion that PTPs display site selectivity in their action on tyrosine kinase receptors.
Copyright © 2004, American Society for Microbiology. All Rights Reserved (Less)
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- author
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular and Cellular Biology
- volume
- 24
- issue
- 5
- pages
- 201 - 2190
- publisher
- American Society for Microbiology
- external identifiers
-
- wos:000189309500032
- scopus:10744231326
- ISSN
- 0270-7306
- DOI
- 10.1128/MCB.24.5.2190-2201.2004
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
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- fd93ef8a-e76c-4d90-8bd3-e680ddbf188c (old id 121754)
- date added to LUP
- 2016-04-01 11:38:29
- date last changed
- 2022-02-03 02:23:24
@article{fd93ef8a-e76c-4d90-8bd3-e680ddbf188c, abstract = {{The platelet-derived growth factor (PDGF) ß receptor mediates mitogenic and chemotactic signals. Like other tyrosine kinase receptors, the PDGF ß receptor is negatively regulated by protein tyrosine phosphatases (PTPs). To explore whether T-cell PTP (TC-PTP) negatively regulates the PDGF ß receptor, we compared PDGF ß receptor tyrosine phosphorylation in wild-type and TC-PTP knockout (ko) mouse embryos. PDGF ß 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 C1 binding site Y1021, previously implicated in chemotaxis, displayed the largest increase in phosphorylation. The increase in Y1021 phosphorylation was accompanied by increased phospholipase C1 activity and migratory hyperresponsiveness to PDGF. PDGF ß receptor tyrosine phosphorylation in PTP-1B ko MEFs but not in PTP 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 ß receptor signaling and support the general notion that PTPs display site selectivity in their action on tyrosine kinase receptors. <br/><br> Copyright © 2004, American Society for Microbiology. All Rights Reserved}}, author = {{Persson, Camilla and Sävenhed, Catrine and Bourdeau, Annie and Tremblay, Michel L and Markova, Boyka and Böhmer, Frank D and Haj, Fawaz G and Neel, Benjamin G and Elson, Ari and Heldin, Carl-Henrik and Rönnstrand, Lars and Ostman, Arne and Hellberg, Carina}}, issn = {{0270-7306}}, language = {{eng}}, number = {{5}}, pages = {{201--2190}}, publisher = {{American Society for Microbiology}}, series = {{Molecular and Cellular Biology}}, title = {{Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase.}}, url = {{https://lup.lub.lu.se/search/files/2574334/623984.pdf}}, doi = {{10.1128/MCB.24.5.2190-2201.2004}}, volume = {{24}}, year = {{2004}}, }