Rho-GTPases are molecular switches that control many aspects of cell biology (Etienne-Mannevilee & Hall 2002). Using specific GTPase exchange factors (GEFs) and GTPase activating factors (GAPs), they cycle between an active (GTP-bound) state and an inactive (GDP-bound) state. The human genome encodes 145 potential RhoGAP and RhoGEF proteins, with varying sets of interaction domains, which can potentially target these proteins to different locations, and allow them to connect upstream and downstream molecules forming transient localized Rho protein signaling platforms. Despite extensive research in the field (e.g. Feltri et al, 2008 , Wells et al, 2006), many of these RhoGAPs/GEFs are poorly characterized, and their contribution to Rho protein signaling specificity is not well understood.
The aim of this database is to improve the understanding of the role of guanine nucleotide exchange factors (GEFs) and GTPase activating factors (GAPs) in controlling the specificity of Rho-GTPase signal transduction.
Müller PM*, Rademacher J*, Bagshaw RD*, Alp MK, Giudice G, Heinrich LE, Barth C, Eccles RL, Sanchez-Castro M, Brandenburg L, Mbamalu G, Tucholska M, Spatt L, Wortmann C, Czajkowski MT, Welke RW, Zhang S, Nguyen V, Rrustemi T, Trnka P, Freitag K, Larsen B, Popp O, Mertins P, Bakal C, Gingras AC, Pertz O, Roth FP, Colwill K, Pawson T, Petsalaki E#, Rocks O#. Systematic characterization of RhoGEF/RhoGAP regulatory proteins reveals organization principles of RhoGTPase signaling. bioRxiv 354316 doi:https://doi.org/10.1101/354316
As a key resource, the laboratory has generated a validated expression library for almost the entire set of full-length human RhoGEFs/GAPs. The interactors included in this database have been found using epitope-tagged immunoprecipitation coupled to tandem Mass Spectrometry (MS/MS) (Hunt et al, 1986). Furthermore we provide imaging data offering contextual information regarding the sub-cellular localization of the RhoGAPs/GEFs upon over-expression (using YFP and CFP tags).
Finally, we have performed the first systematic screen of RhoGAP/GEF specificity for RhoA, Rac1 and Cdc42.
Our database also includes information from several other databases: