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ID: 6046.0, MPI für molekulare Physiologie / Sonstige wissenschaftliche Organisationseinheiten
Characterisation of PDZ-GEFs, a family of guanine nucleotide exchange factors specific for Rap1 and Rap2
Authors:Kuiperij, H. Bea; De Rooij, Johan; Rehmann, Holger; van Triest, Miranda; Wittinghofer, Alfred; Bos, Johannes L.; Zwartkruis, Fried J. T.
Research Context:nucleotide exchange factors
Date of Publication (YYYY-MM-DD):2003-02-17
Title of Journal:Biochimica et Biophysica Acta - Molecular Cell Research
Journal Abbrev.:Biochim. Biophys. Acta - Mol. Cell Res.
Issue / Number:2-3
Start Page:141
End Page:149
Sequence Number of Article:1
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:PDZ-GEF1 (RA-GEF/nRapGEP/CNrasGEF) is a guanine nucleotide exchange factor (GEF) characterised by the presence of a PSD- 95/DlgA/ZO-1 (PDZ) domain, a Ras-association (RA) domain and a region related to a cyclic nucleotide binding domain (RCBD). These domains are in addition to a Ras exchange motif (REM) and GEF domain characteristic for GEFs for Ras-like small GTPases. PDZ-GEF1 efficiently exchanges nucleotides of both Rap I and Rap2, but has also been implicated in mediating cAMP-induced Ras activation through binding of cAMP to the RCBD. Here we describe a new family member, PDZ-GEF2, of which we isolated two splice variants (PDZ-GEF2A and 213). PDZ-GEF2 contains, in addition to the domains characteristic for PDZ-GEF1, a second, less conserved RCBD at the N-terminus. PDZ-GEF2 is also specific for both Rap I and Rap2. We further investigated the possibility that PDZ-GEF2, like PDZ-GEF1, is a cAMP-responsive GEF for Ras. However, in contrast to previous results, we did not find any effect of either PDZ-GEF1 or PDZ-GEF2 on Ras in the absence or presence of cAMP. Moreover, affinity measurements by isothermic calorimetry showed that the RCBD of PDZ-GEF1 does not bind cAMP with a physiologically relevant affinity. We conclude that both PDZ-GEF1 and 2 are specific for Rap1 and Rap2 and unresponsive to cAMP and various other nucleotides. (C) 2002 Elsevier Science B.V. All rights reserved.
Free Keywords:cAMP; Ras; Rap; guanine nucleotide exchange factor
Last Change of the Resource (YYYY-MM-DD):2002-09-30
External Publication Status:published
Document Type:Article
Communicated by:Jürgen Block
Affiliations:MPI für molekulare Physiologie/Sonstige Wissenschaftliche Organisationseinheiten/Emeritus-AG: Prof. Dr. Alfred Wittinghofer
External Affiliations:Univ Utrecht, Ctr Med, Dept Physiol Chem, Univ Weg 100, NL-3584; CG Utrecht, Netherlands;
Univ Utrecht, Ctr Med, Ctr Biomed Genet, NL-3584 CG Utrecht, Netherlands
Identifiers:URL:http://dx.doi.org/10.1016/S0167-4889(02)00365-8 [full text of this article]
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