title: Proteomic analysis of Rac1 signaling regulation by guanine nucleotide exchange factors.
abstract: The small GTPase Rac1 is implicated in various cellular processes that are essential for normal cell function. Deregulation of Rac1 signaling 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 2 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 signaling cascades that might account for the GEF-mediated Rac1-driven cellular effects.
authors.affiliation: a Cell Signaling Group, Cancer Research UK Manchester Institute, The University of Manchester , Manchester , UK.
authors.forename: Hadir
authors.initials: H
authors.lastname: Marei
authors.affiliation: b Proteome Center Tuebingen, Interfaculty Institute for Cell Biology, University of Tuebingen , Tuebingen , Germany.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Carpy
authors.affiliation: b Proteome Center Tuebingen, Interfaculty Institute for Cell Biology, University of Tuebingen , Tuebingen , Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Macek
authors.affiliation: a Cell Signaling Group, Cancer Research UK Manchester Institute, The University of Manchester , Manchester , UK.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Malliri
mesh_terms: D000818:Animals; D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding; D025941:Protein Interaction Mapping; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins; D020830:rac1 GTP-Binding Protein
keywords: Guanine nucleotide Exchange Factors (GEFs); IQGAP1; Ingenuity Integrated Pathway Analysis (IPA); P-Rex1; Rac1; Small GTPases; Stable Isotope Labeling by Amino acids in Cell culture (SILAC); TMOD3; Tandem Affinity Purification (TAP); Tiam1