Cell Biology

SOS Coordinates the Action

Science's STKE  15 Jan 2002:
Vol. 2002, Issue 115, pp. tw17
DOI: 10.1126/stke.2002.115.tw17

Son of sevenless (SOS) is a guanine nucleotide exchange factor (GEF) well known for its involvement in activating the guanosine triphosphatase (GTPase) Ras in response to receptor tyrosine kinase activation. Innocenti et al. suggest that SOS-1 is also a GEF for the GTPase Rac. These two different GEF activities may be important for coordinate regulation of Ras and Rac in response to growth factor stimuli. SOS-1 competitively interacted in vivo and in vitro with either Grb2 (the adaptor for Ras signaling) or another signaling adaptor E3b1. The SOS-E3b1 complex bound a third molecule Eps8 that was essential for SOS-1-mediated Rac activation. The relative abundance of Grb2 and E3b1 were quite different (10 times as much Grb2 as E3b1) in the cells tested, and increasing the levels of E3b1 inhibited Ras signaling and promoted Rac activation. Direct activation of Rac by SOS-1 depended on the presence of Eps8. Kinetic analysis of the interaction of SOS-1 with the platelet-derived growth factor (PDGF) receptor and with E3b1 after PDGF treatment suggested that the receptor-Grb2-SOS interaction was transient and decreased after receptor activation, whereas the E3b1-SOS-1 interaction persisted after PDGF treatment. Activation of Ras was also transient and diminished after 3 min, whereas activation of Rac persisted for at least 15 min after PDGF treatment. Thus, cellular responses to growth factors may be coordinated temporally by the transition of SOS complexes at the receptor associated with Ras activation to SOS complexes distant from the receptor associated with Rac activation.

M. Innocenti, P. Tenca, E. Frittoli, M. Faretta, A. Tocchetti, P. P. Di Fiore, G. Scita, Mechanisms through which Sos-1 coordinates the activation of Ras and Rac. J. Cell Biol. 156, 125-136 (2002). [Abstract] [Full Text]