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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
47
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pubmed:dateCreated |
2004-11-15
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pubmed:abstractText |
The Rho-GTPase Cdc42 is important for the establishment and maintenance of epithelial polarity. Signaling from Cdc42 is propagated via its effector molecules that specifically bind to Cdc42 in the GTP-bound form. The cell-cell contact regulator and actin-binding protein IQGAP1 is described as effector of Cdc42 and Rac. Unexpectedly, we show in this study that IQGAP1 bound also directly nucleotide-depleted Cdc42 (Cdc42-ND). This interaction was enhanced in the presence of phosphatase inhibitors and in epithelial cells without cell-cell contacts. Tandem mass spectrometry analysis and immunoprecipitation experiments revealed that IQGAP1 was Ser1443-phosphorylated in vivo, potentially by protein kinase Cepsilon and upon loss of cell-cell contacts. In addition, we identified two independent domains of the IQGAP1 C terminus that bound exclusively Cdc42-ND. These domains interacted with each other, favoring the binding to Cdc42-GTP. Moreover, phosphorylation on Ser1443 strongly inhibited this intramolecular interaction. Thus, we unraveled a molecular mechanism that reveals a novel type of Rho-GTPase regulator. We propose that, depending on its phosphorylation state, IQGAP1 might serve as an effector or sequester nucleotide-free Cdc42 to prevent signaling.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Buffers,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotide Exchange Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/IQ motif containing GTPase...,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/PRKCE protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-epsilon,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/cdc42 GTP-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/rac1 GTP-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/ras GTPase-Activating Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/rho GTP-Binding Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
48495-504
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15355962-Algorithms,
pubmed-meshheading:15355962-Amino Acid Sequence,
pubmed-meshheading:15355962-Binding Sites,
pubmed-meshheading:15355962-Blotting, Western,
pubmed-meshheading:15355962-Buffers,
pubmed-meshheading:15355962-Cell Communication,
pubmed-meshheading:15355962-Cell Line,
pubmed-meshheading:15355962-Cell Line, Tumor,
pubmed-meshheading:15355962-Gene Expression Regulation,
pubmed-meshheading:15355962-Glutathione Transferase,
pubmed-meshheading:15355962-Guanine Nucleotide Exchange Factors,
pubmed-meshheading:15355962-Guanosine Diphosphate,
pubmed-meshheading:15355962-Guanosine Triphosphate,
pubmed-meshheading:15355962-Humans,
pubmed-meshheading:15355962-Immunoprecipitation,
pubmed-meshheading:15355962-Mass Spectrometry,
pubmed-meshheading:15355962-Molecular Sequence Data,
pubmed-meshheading:15355962-Mutagenesis,
pubmed-meshheading:15355962-Nucleotides,
pubmed-meshheading:15355962-Oligonucleotides,
pubmed-meshheading:15355962-Phosphorylation,
pubmed-meshheading:15355962-Plasmids,
pubmed-meshheading:15355962-Protein Binding,
pubmed-meshheading:15355962-Protein Conformation,
pubmed-meshheading:15355962-Protein Kinase C,
pubmed-meshheading:15355962-Protein Kinase C-epsilon,
pubmed-meshheading:15355962-Protein Structure, Tertiary,
pubmed-meshheading:15355962-Recombinant Proteins,
pubmed-meshheading:15355962-Sequence Homology, Amino Acid,
pubmed-meshheading:15355962-Serine,
pubmed-meshheading:15355962-Signal Transduction,
pubmed-meshheading:15355962-Software,
pubmed-meshheading:15355962-Time Factors,
pubmed-meshheading:15355962-cdc42 GTP-Binding Protein,
pubmed-meshheading:15355962-rac1 GTP-Binding Protein,
pubmed-meshheading:15355962-ras GTPase-Activating Proteins,
pubmed-meshheading:15355962-rho GTP-Binding Proteins
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pubmed:year |
2004
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pubmed:articleTitle |
Phosphorylation of IQGAP1 modulates its binding to Cdc42, revealing a new type of rho-GTPase regulator.
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pubmed:affiliation |
ETH-Zürich, Institute of Biochemistry, Schafmattstrasse 18, Zürich 8093, Switzerland and Friedrich Miescher Institute, Basel 4002, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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