Regulation
GEFs are often recruited by adaptor proteins in response to upstream signals. GEFs are multi-domain proteins and interact with other proteins inside the cell through these domains. Adaptor proteins can modulate GEF activity by interacting with other domains besides the catalytic domain. For example, SOS1, the Ras GEF in the MAPK/ERK pathway, is recruited by the adaptor protein GRB2 in response to EGF receptor activation. The binding of SOS1 to GBR2 localizes it to the plasma membrane, where it can activate the membrane bound Ras. Other GEFs, such as the Rho GEF Vav1, are activated upon phosphorylation in response to upstream signals. Secondary messengers such as cAMP and calcium can also play a role in GEF activation.
Crosstalk has also been shown between GEFs and multiple GTPase signaling pathways. For example, SOS contains a Dbl homology domain in addition to its CDC25 catalytic domain. SOS can act as a GEF to activate Rac1, a RhoGTPase, in addition to its role as a GEF for Ras. SOS is therefore a link between the Ras-Family and Rho-Family GTPase signaling pathways.
Read more about this topic: Guanine Nucleotide Exchange Factor
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