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Mutation of a Src p...
Mutation of a Src phosphorylation site in the PDGF beta-receptor leads to increased PDGF-stimulated chemotaxis but decreased mitogenesis
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- Hansen, Klaus (författare)
- Ludwiginstitutet för Cancerforskning
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- Johnell, Matilda (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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- Siegbahn, Agneta (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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- Rorsman, Charlotte (författare)
- Ludwiginstitutet för Cancerforskning
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- Engström, Ulla (författare)
- Ludwiginstitutet för Cancerforskning
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- Wernstedt, Christer (författare)
- Ludwiginstitutet för Cancerforskning
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- Heldin, Carl-Henrik (författare)
- Ludwiginstitutet för Cancerforskning
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- Rönnstrand, Lars (författare)
- Ludwiginstitutet för Cancerforskning
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(creator_code:org_t)
- 1996
- 1996
- Engelska.
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Ingår i: EMBO Journal. - 0261-4189 .- 1460-2075. ; 15:19, s. 5299-5313
- Relaterad länk:
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- 1-Phosphatidylinositol 3-Kinase
- Chemotaxis
- Phospholipase C
- Platelet-Derived Growth Factor
- MEDICINE
- MEDICIN
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- art (ämneskategori)
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