RasGEF1A and RasGEF1B are guanine nucleotide exchange factors that discriminate between Rap GTP-binding proteins and mediate Rap2-specific nucleotide exchange

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dc.citation.epage4616en_US
dc.citation.issueNumber16en_US
dc.citation.spage4607en_US
dc.citation.volumeNumber276en_US
dc.contributor.authorYaman, E.en_US
dc.contributor.authorGasper, R.en_US
dc.contributor.authorKoerner, C.en_US
dc.contributor.authorWittinghofer, A.en_US
dc.contributor.authorTazebay, U. H.en_US
dc.date.accessioned2016-02-08T10:03:09Z
dc.date.available2016-02-08T10:03:09Z
dc.date.issued2009en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractThe highly conserved RasGEF1 family of proteins contain a C-terminal CDC25-Ras exchange motif domain and an N-terminal RasGEF-N domain, and are of unknown function and specificity. Using purified RasGEF1A and RasGEF1B proteins, as well as Ras family proteins, we established that RasGEF1A and RasGEF1B function as very specific exchange factors for Rap2, a member of the Rap subfamily of Ras-like G-proteins. They do not act on Rap1 or other members of the Ras subfamily. Although Rap2 was implicated in the regulation of cell adhesion, the establishment of cell morphology, and the modulation of synapses in neurons, no specific guanine nucleotide exchange factor for Rap2 was previously identified. Using reciprocal site-directed mutagenesis, we analyzed residues that allow RasGEF1 proteins to discriminate between Rap1 and Rap2, and we were able to identify Phe39 in the switch I region of Rap2 as a specificity residue. Mutation of the corresponding Ser39 in Rap1 changed the specificity and allowed the nucleotide exchange of Rap1(S39F) to be stimulated by RasGEF1B. © 2009 FEBS.en_US
dc.identifier.doi10.1111/j.1742-4658.2009.07166.xen_US
dc.identifier.issn1742-464X
dc.identifier.urihttp://hdl.handle.net/11693/22668
dc.language.isoEnglishen_US
dc.publisherWiley-Blackwell Publishing Ltd.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1111/j.1742-4658.2009.07166.xen_US
dc.source.titleFEBS Journalen_US
dc.subjectG-proteinsen_US
dc.subjectGuanine nucleotide exchangeen_US
dc.subjectRap2en_US
dc.subjectRas familyen_US
dc.subjectRasGEF1en_US
dc.subjectGuanine nucleotide exchange factoren_US
dc.titleRasGEF1A and RasGEF1B are guanine nucleotide exchange factors that discriminate between Rap GTP-binding proteins and mediate Rap2-specific nucleotide exchangeen_US
dc.typeArticleen_US

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