Platelet-derived growth factor-induced signaling pathways interconnect to regulate the temporal pattern of Erk1/2 phosphorylation
2011 (English)In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 23, no 1, 280-287 p.Article in journal (Refereed) Published
The biological outcome of Erk1/2 activation is specified by the duration and magnitude of its phosphorylation, as well as its subcellular localization. In the present study, we investigated how the cross-talk between signaling pathways induced by platelet-derived growth factor receptor beta (PDGFR beta) regulates the temporal pattern of Erk1/2 activation. We demonstrated that Src kinase activity was necessary for rapid Erk1/2 phosphorylation in PDGF-BB-stimulated cells. A delay in the onset of Erk1/2 activation was also observed upon phospholipase C (PLC) inhibition; this effect was found to be mediated by protein kinase C (PKC). In addition, we observed that both the PI3K pathway and RasGAP negatively regulated the strength of Erk1/2 phosphorylation. In contrast, interfering with SHP2 binding to PDGFR beta did not affect the pattern of Erk1/2 activation. Interestingly, changes in the kinetics and amplitude of Erk1/2 activation were transmitted to the transcriptional level and affected c-fos expression. In conclusion, cross-talk with other PDGFR beta-induced signaling pathways is important for fine-tuning of the pattern of Erk1/2 activation.
Place, publisher, year, edition, pages
2011. Vol. 23, no 1, 280-287 p.
Erk1/2, PDGF, Src, PI3K, PLC, Cross-talk
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-139352DOI: 10.1016/j.cellsig.2010.09.013ISI: 000284444600032OAI: oai:DiVA.org:uu-139352DiVA: diva2:381048