Growth Factor Receptors, Rac1, and STAT3

Science's STKE  10 Oct 2000:
Vol. 2000, Issue 53, pp. tw4
DOI: 10.1126/stke.2000.53.tw4

The STAT (signal transducers and activators of transcription) transcription factors are activated in response to cytokine receptors and associated kinases. The STATs then migrate to the nucleus where they regulate transcription of specific genes. Stimulation of growth factor receptors also activates STATs, but the mechanism by which this occurs is not well understood. Simon et al. show that STAT3 is activated in response to the small guanine nucleotide-binding protein Rac1. In fact, direct binding interaction of activated (but not inactive) Rac1 with STAT3 appears to contribute to STAT activation. The studies indicate that Rac functions in growth factor-induced activation of STAT3 in two ways. It apparently helps localize STAT3 to kinase complexes at the cell surface and also promotes activation of kinases, like Jak2, that phosphorylate STAT3. The results help clarify control of STAT3, which along with Rac (through cooperation with Ras) can contribute to cell transformation and cancer.

Simon, A.R., Vikis, H.G., Stewart, S., Fanburg, B.L., Cochram, B.H., and Guan, K.-L. (2000) Regulation of STAT3 by direct binding to the Rac1 GTPase. Science 290: 144-147. [Abstract] [Full Text]