Src, New Tricks for an Old Kinase

Science's STKE  22 Feb 2000:
Vol. 2000, Issue 20, pp. tw10
DOI: 10.1126/stke.2000.20.tw10

The non-receptor protein tyrosine kinase Src has been extensively studied to elucidate its role in normal cellular processes. It is widely expressed in tissues and propagates signals transmitted by growth factor receptors. Src is critical for such diverse functions as proliferation, differentiation, cellular adhesion, and locomotion. To these functions, we can now add angiogenesis and apoptotic regulation. Schlessinger reviews the latest observations that inactive Src exists in a complex with TRAF6. Activation of the cell death-sparing TRANCE receptor effects the recruitment of the TRAF6/Src complex and the subsequent activation of Src. Additionally, TRANCE-dependent Src activation of Akt leads to greater activation of anti-apoptotic pathways, as compared to Src-deficient cells. Schlessinger also discusses the finding that Src protects cells from apoptosis during vascular endothelial growth factor (VEGF)-dependent angiogenesis in mice and chick embryos. Expression of catalytically inactive Src blocks angiogenesis and retards the growth of VEGF-expressing tumors. Different mechanisms are used by TRANCE and VEGF to activate Src; however, both appear to occur through derepression of the intramolecularly inactive conformation of Src.

Schlessinger, J. (2000) New roles for src kinases in control of cell survival and angiogenesis. Cell 100: 293-296. [Online Journal]