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Mutation of a Src phosphorylation site in the PDGF beta-receptor leads to increased PDGF-stimulated chemotaxis but decreased mitogenesis
Ludwiginstitutet för Cancerforskning.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Ludwiginstitutet för Cancerforskning.
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1996 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 15, no 19, 5299-5313 p.Article in journal (Refereed) Published
Abstract [en]

Ligand induced activation of the beta-receptor for platelet-derived growth factor (PDGF) leads to activation of Src family tyrosine kinases. We have explored the possibility that the receptor itself is a substrate for Src. We show that Tyr934 in the kinase domain of the PDGF receptor is phosphorylated by Src. Cell lines expressing a beta-receptor mutant, in which Tyr934 was replaced with a phenyalanine residue, showed reduced mitogenic signaling in response to PDGF-BB. In contrast, the mutant receptor mediated increased signals for chemotaxis and actin reorganization. Whereas the motility responses of cells expressing wild-type beta-receptors were attenuated by inhibition of phosphatidylinositol 3'-kinase, those of cells expressing the mutant receptor were only slightly influenced. In contrast, PDGF-BB-induced chemotaxis of the cells with the mutant receptor was attenuated by inhibition of protein kinase C, whereas the chemotaxis of cells expressing the wild-type beta-receptor was less affected. Moreover, the PDGF-BB-stimulated tyrosine phosphorylation of phospholipase C-gamma was increased in the mutant receptor cells compared with wild-type receptor cells. In conclusion, the characteristics of the Y934F mutant suggest that the phosphorylation of Tyr934 by Src negatively modulates a signal transduction pathway leading to motility responses which involves phospholipase C-gamma, and shifts the response to increased mitogenicity.

Place, publisher, year, edition, pages
1996. Vol. 15, no 19, 5299-5313 p.
Keyword [en]
1-Phosphatidylinositol 3-Kinase, Chemotaxis, Phospholipase C, Platelet-Derived Growth Factor
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-72755PubMedID: 8895575OAI: oai:DiVA.org:uu-72755DiVA: diva2:100666
Available from: 2005-05-31 Created: 2005-05-31 Last updated: 2010-11-09Bibliographically approved

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Johnell, MatildaSiegbahn, AgnetaRorsman, CharlotteEngström, UllaWernstedt, ChristerHeldin, Carl-Henrik
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