Editors' ChoiceGrowth Factors

Sharing the PDGF Receptor

Science's STKE  15 May 2007:
Vol. 2007, Issue 386, pp. tw167
DOI: 10.1126/stke.3862007tw167

Ball et al. report that both vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) stimulate migration and proliferation of human adult mesenchymal stem cells (from bone marrow) and human dermal fibroblasts. Surprisingly, these two cell types lacked any detectable VEGF receptors (VEGFRs)--no transcripts were detected by reverse transcription polymerase chain reaction, and no proteins were detected by fluorescence-activated cell sorting. Experiments with function-blocking antibodies, selective pharmacological receptor tyrosine kinase inhibitors, or short-interfering RNAs indicated that VEGF signaled through the PDGF receptors PDGFRα and PDGFRβ. Analysis of receptor tyrosine kinase phosphorylation in response to VEGF using an array of 42 specific antibodies showed that VEGF stimulated the phosphorylation of PDGFRα and PDGFRβ, as well as stimulating the phosphorylation of the epidermal growth factor receptor, EphA7, and of Ax1. The stimulation of PDGFRs by VEGF appeared to be direct, because VEGF did not stimulate production of PDGF, and chemical cross-linking studies showed that VEGF bound to PDGFRα and PDGFRβ. Pretreatment of cells with VEGF inhibited the migration of the cells toward PDGF, which suggests that VEGF may attenuate responses to PDGF. Thus, VEGF targets are not limited to cells expressing VEGFRs.

S. G. Ball, C. A. Shuttleworth, C. M. Kielty, Vascular endothelial growth factor can signal through platelet-derived growth factor receptors. J. Cell Biol. 177, 489-500 (2007). [Abstract] [Full Text]