کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1963781 1058504 2010 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mutation of tyrosine residue 857 in the PDGF β-receptor affects cell proliferation but not migration
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Mutation of tyrosine residue 857 in the PDGF β-receptor affects cell proliferation but not migration
چکیده انگلیسی

Activation of platelet-derived growth factor (PDGF) receptors occurs through ligand-induced dimerization and autophosphorylation. In this study, we investigated the effects of mutation of tyrosine residue 857 (Y857) in the activation loop of the PDGF β-receptor (PDGFRβ) to phenylalanine (Y857F). In agreement with previous observations, we found that PDGFRβY857F had a severely diminished in vitro kinase activity. However, in vivo the overall amount of tyrosine phosphorylation of PDGFRβY857F was similar to that of the wild-type receptor, except for the tyrosine residue 771 (Y771) which displayed a stronger phosphorylation in the mutant receptor. Analysis of the ability to induce signal transduction revealed that the PDGFRβY857F mutant had an attenuated activation of Akt and Erk1/2 MAP kinase. In contrast, the mutant receptor efficiently mediated phosphorylation of the ubiquitin-ligase c-Cbl that participates in receptor internalization and degradation, and PLCγ which has previously been shown to be connected with various cellular responses, including migration. However, the protein tyrosine phosphatase SHP-2, implicated in the PDGF-induced mitogenic response, together with the adaptor proteins Alix and Stam, involved in intracellular sorting of receptor, was not phosphorylated in cells expressing PDGFRβY857F. We found that both receptor variants were internalized from the cell surface and degraded at a comparable rate. Interestingly, PDGFRβY857F was unable to mediate PDGF-BB-induced mitogenic signaling, whereas it could elicit a chemotactic response.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 22, Issue 9, September 2010, Pages 1363–1368
نویسندگان
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