The complex life of a GEF

Receptor tyrosine kinases (RTKs) that are bound to appropriate growth factors activate PI3K, which initiates Rac-induced cytoskeletal alterations. The signaling steps between PI3K and Rac are uncovered on page 17 in an article by Innocenti et al. that reveals the importance of complexes in activating guanine nucleotide exchange factors (GEFs).

Genetic evidence has supported the involvement of the GEF Sos-1 for stimulating Rac activity in response to growth factors. Sos-1 is found in complex with Abi1 and Eps8, and interference with any of these proteins is known to block actin remodeling in response to RTK activation. Innocenti et al. now show biochemically that Sos-1 is indeed the GEF that activates Rac in response to PI3K.

Full GEF activation was a stepwise process. The physical presence of PI3K itself stimulated low levels...