ena-STUDY-MAX DELBRUECK CENTER FOR MOLECULAR MEDICINE-07-06-2018-15:00:06:692-3757
Systematic study of mammalian RhoGAPs and GEFs and their role in regulating Rho signalling
Rho-GTPases are molecular switches that control many critical aspects of cell biology.  With the help of GTPase exchange factors (GEFs) and GTPase activating factors (GAPs), they cycle between an active (GTP-bound) state and an inactive (GDP-bound) state.  While the human genome encodes ~20 RhoGTPases, there are over 140 potential RhoGAP and RhoGEF proteins.  These have widely varying sets of interaction domains, which can potentially target these proteins to different subcellular locations, and allow them to connect upstream and downstream molecules to form transient localized Rho signaling platforms. Despite extensive research in the field, many of these RhoGAPs/GEFs are poorly characterized, and their contributions to signaling pathways and cell dynamics are not well understood.  Thus, we have undertaken a systematic approach to study these regulatory proteins, with the aim to understand their role in controlling Rho signaling specificity.  Our approach involves the integration of proteomics, specificity and imaging data, to identify potential RhoGAP/GEFs regulators and targets, their localization and the effect of their overexpression on cell phenotype.  Our data, along with information from diverse databases, enables us to compile an integrated network, providing a new resource for studying the roles of Rho-GTPases and their GEFs and GAPs in cell mechanisms.
Rho-GTPases are molecular switches that control many critical aspects of cell biology.  With the help of GTPase exchange factors (GEFs) and GTPase activating factors (GAPs), they cycle between an active (GTP-bound) state and an inactive (GDP-bound) state.  While the human genome encodes ~20 RhoGTPases, there are over 140 potential RhoGAP and RhoGEF proteins.  These have widely varying sets of interaction domains, which can potentially target these proteins to different subcellular locations, and allow them to connect upstream and downstream molecules to form transient localized Rho signaling platforms. Despite extensive research in the field, many of these RhoGAPs/GEFs are poorly characterized, and their contributions to signaling pathways and cell dynamics are not well understood.  Thus, we have undertaken a systematic approach to study these regulatory proteins, with the aim to understand their role in controlling Rho signaling specificity.  Our approach involves the integration of proteomics, specificity and imaging data, to identify potential RhoGAP/GEFs regulators and targets, their localization and the effect of their overexpression on cell phenotype.  Our data, along with information from diverse databases, enables us to compile an integrated network, providing a new resource for studying the roles of Rho-GTPases and their GEFs and GAPs in cell mechanisms.