Mutation of tyrosine residue 857 in the PDGF β-receptor affects cell proliferation but not migration
2010 (English)In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 22, no 9, 1363-1368 p.Article in journal (Refereed) Published
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 beta-receptor (PDGFR beta) to phenylalanine (Y857F). In agreement with previous observations, we found that PDGFR beta(Y857F) had a severely diminished in vitro kinase activity. However, in vivo the overall amount of tyrosine phosphorylation of PDGFR beta(Y857F) 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 PDGFR beta(Y857F) 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 PLC gamma 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 PDGFR beta(Y857F). We found that both receptor variants were internalized from the cell surface and degraded at a comparable rate. Interestingly, PDGFR beta(Y857F) was unable to mediate PDGF-BB-induced mitogenic signaling, whereas it could elicit a chemotactic response.
Place, publisher, year, edition, pages
2010. Vol. 22, no 9, 1363-1368 p.
PDGF; Y857; Autophosphorylation; SHP-2; Proliferation; Chemotaxis
Cell and Molecular Biology Cell and Molecular Biology Cell and Molecular Biology
Research subject Biology with specialization in Molecular Cell Biology
IdentifiersURN: urn:nbn:se:uu:diva-122471DOI: 10.1016/j.cellsig.2010.05.004ISI: 000279889300011OAI: oai:DiVA.org:uu-122471DiVA: diva2:310211