| The guanine nucleotide exchange factor CNrasGEF activates ras in response to cAMP and cGMP. | |
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MedLine Citation:
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PMID: 10801446 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Small GTPase proteins such as Ras are key regulators of cellular proliferation and are activated by guanine nucleotide exchange/releasing factors (GEFs/GRFs). Three classes of Ras GRFs have been identified to date, represented by Sos1/2, Ras-GRF1/2 and Ras-GRP. Here, we describe a novel candidate Ras activator, cyclic nucleotide rasGEF (CNrasGEF), which contains CDC25, Ras exchange motif (REM), Ras-association (RA), PDZ and cNMP (cAMP/cGMP) binding (cNMP-BD) domains, two PY motifs and a carboxy-terminal SxV sequence. CNrasGEF can activate Ras in vitro, and it binds cAMP directly via its cNMP-BD. In cells, CNrasGEF activates Ras in response to elevation of intracellular cAMP or cGMP, or treatment with their analogues 8-Br-cAMP or 8-Br-cGMP, independently of protein kinases A and G (PKA and PKG). This activation is prevented in CNrasGEF lacking its CDC25 domain or cNMP-BD. CNrasGEF can also activate the small GTPase Rap1 in cells, but this activation is constitutive and independent of cAMP. CNrasGEF is expressed mainly in the brain and is localized at the plasma membrane, a localization dependent on the presence of intact PDZ domain but not the SxV sequence. These results suggest that CNrasGEF may directly connect cAMP-generating pathways or cGMP-generating pathways to Ras. |
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Authors:
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N Pham; I Cheglakov; C A Koch; C L de Hoog; M F Moran; D Rotin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Current biology : CB Volume: 10 ISSN: 0960-9822 ISO Abbreviation: Curr. Biol. Publication Date: 2000 May |
Date Detail:
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Created Date: 2000-09-20 Completed Date: 2000-09-20 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9107782 Medline TA: Curr Biol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 555-8 Citation Subset: IM |
Affiliation:
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Program in Cell Biology, Department of Biochemistry, The Hospital for Sick Children, University of Toronto, Toronto, M5G 1X8, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line, Transformed Cyclic AMP / metabolism* Cyclic AMP-Dependent Protein Kinases / metabolism Cyclic GMP / metabolism* Drosophila Humans Rats rap1 GTP-Binding Proteins / metabolism ras Guanine Nucleotide Exchange Factors / genetics, metabolism* ras Proteins / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/ras Guanine Nucleotide Exchange Factors; 60-92-4/Cyclic AMP; 7665-99-8/Cyclic GMP; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 3.6.5.2/rap1 GTP-Binding Proteins; EC 3.6.5.2/ras Proteins |
| Comments/Corrections | |
Erratum In:
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Curr Biol 2000 Jul 27-Aug 10;10(15):R577-8 |
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