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  Characterisation of PDZ-GEFs, a family of guanine nucleotide exchange factors specific for Rap1 and Rap2

Kuiperij, H. B., De Rooij, J., Rehmann, H., van Triest, M., Wittinghofer, A., Bos, J. L., et al. (2003). Characterisation of PDZ-GEFs, a family of guanine nucleotide exchange factors specific for Rap1 and Rap2. Biochimica et Biophysica Acta - Molecular Cell Research, 1593(2-3): 1, pp. 141-149. Retrieved from http://dx.doi.org/10.1016/S0167-4889(02)00365-8.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0014-0CB2-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0014-0CB3-A
Genre: Journal Article
Alternative Title : Biochim. Biophys. Acta - Mol. Cell Res.

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 Creators:
Kuiperij, H. Bea, Author
De Rooij, Johan, Author
Rehmann, Holger1, Author
van Triest, Miranda, Author
Wittinghofer, Alfred2, Author              
Bos, Johannes L., Author
Zwartkruis, Fried J. T., Author
Affiliations:
1Max Planck Institute of Molecular Physiology, Max Planck Society, ou_1753286              
2Sonstige Wissenschaftliche Organisationseinheiten, Max Planck Institute of Molecular Physiology, Max Planck Society, ou_1753294              

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Free keywords: cAMP; Ras; Rap; guanine nucleotide exchange factor
 Abstract: 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.

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Language(s): eng - English
 Dates: 2002-09-302003-02-17
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
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Title: Biochimica et Biophysica Acta - Molecular Cell Research
  Alternative Title : Biochim. Biophys. Acta - Mol. Cell Res.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 1593 (2-3) Sequence Number: 1 Start / End Page: 141 - 149 Identifier: -