Editors' ChoiceDevelopment

Summation of PDGF Receptor Signals

STKE  09 Jan 2001:
Vol. 2001, Issue 64, pp. tw6
DOI: 10.1126/stke.2001.64.tw6

Activation of the platelet-derived growth factor receptor (PDGFR) is required for normal vascular development in mice. The receptor transduces signals through the recruitment of molecules including phospholipase C-γ (PLC-γ) and phosphatidylinositol 3-kinase (PI3K). Mice expressing a mutant form of the PDGFR-β isoform that does not bind to PI3K show no developmental defects, and fibroblasts derived from these mice show little defect in proliferation or migration. Now, Tallquist et al. have generated mice bearing a PDGFR-β that does not bind to either PI3K or PLC-γ. Although these mice also displayed no apparent phenotype, biochemical analysis of cells derived from them exhibited reduced proliferation and migration in response to PDGF. Hence, although these two signaling pathways do not appear necessary for development or survival of the mice, their absence results in an attenuated response to ligand stimulation. It may be that a summation of signals transmitted from the PDGFR, rather than a unique signal from an individual pathway, is required to promote a specific cellular function.

Tallquist, M.D., Klinghoffer, R.A., Heuchel, R., Mueting-Nelsen, P.F., Corrin, P.D., Heldin, C.-H., Johnson, R.J., and Soriano, P. (2000) Retention of PDGFR-β function in mice in the absence of phosphatidylinositol 3'-kinase and phospholipase C-γ signaling pathways. Genes Dev. 14: 3179-3190. [Abstract] [Full Text]