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SHP-2 binds to Tyr7...
SHP-2 binds to Tyr763 and Tyr1009 in the PDGF β-receptor and mediates PDGF-induced activation of the Ras/MAP kinase pathway and chemotaxis
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- Rönnstrand, Lars (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Arvidsson, Ann-Kristin (author)
- Uppsala universitet,Institutionen för medicinsk farmakologi
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- Kallin, Anders (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Rorsman, Charlotte (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Hellman, Ulf (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Engström, Ulla (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Wernstedt, Christer (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Heldin, Carl-Henrik (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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(creator_code:org_t)
- Stockton Press, 1999
- 1999
- English.
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In: Oncogene. - : Stockton Press. - 0950-9232. ; 18:25, s. 3696-3702
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
Close
- Activation of the beta-receptor for platelet-derived growth factor (PDGF) by its ligand leads to autophosphorylation on a number of tyrosine residues. Here we show that Tyr763 in the kinase insert region is a novel autophosphorylation site, which after phosphorylation binds the protein tyrosine phosphatase SHP-2. SHP-2 has also previously been shown to bind to phosphorylated Tyr1009 in the PDGF beta-receptor. Porcine aortic endothelial (PAE) cells transfected with a PDGF beta-receptor in which Tyr763 and Tyr1009 were mutated to phenylalanine residues failed to associate with SHP-2 after ligand stimulation. Moreover, PDGF-BB-induced Ras GTP-loading and Erk2 activation were severely compromised in the receptor mutant. Whereas the mitogenic response to PDGF-BB remained at the same level as in cells expressing wild-type PDGF beta-receptor, chemotaxis induced by PDGF-BB was significantly decreased in the case of the Y763F/Y1009F mutant cells, suggesting an important role for SHP-2 in chemotactic signaling.
Keyword
- PDGF beta-receptor; SHP-2; chemotaxis; Ras/MAP kinase pathway
Publication and Content Type
- ref (subject category)
- art (subject category)
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