Proteomic Analysis of Rac1 Signalling Regulation by Guanine Nucleotide Exchange Factors

The small GTPase Rac1 is implicated in various cellular processes that are essential for normal cell function. Deregulation of Rac1 signalling has also been linked to a number of diseases, including cancer. The diversity of Rac1 functioning in cells is mainly attributed to its ability to bind to a multitude of downstream effectors following activation by Guanine nucleotide Exchange Factors (GEFs). Despite the identification of a large number of Rac1 binding partners, factors influencing downstream specificity are poorly defined, thus hindering the detailed understanding of both Rac1's normal and pathological functions. In a recent study we demonstrated a role for two Rac-specific GEFs, Tiam1 and P-Rex1 in mediating Rac1 anti- versus pro-migratory effects, respectively. Importantly, via conducting a quantitative proteomic screen we identified distinct changes in the Rac1 interactome following activation by either GEF indicating that these opposing effects are mediated through GEF modulation of the Rac1 interactome. Here we present the full list of identified Rac1 interactors together with functional annotation of the differentially regulated Rac1 binding partners. In light of this data we also provide additional insights into known and novel signalling cascades that might account for the GEF-mediated Rac1-driven cellular effects.