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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2004-7-20
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pubmed:databankReference |
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pubmed:abstractText |
An important signaling pathway to the actin cytoskeleton links the Rho family GTPase Cdc42 to the actin-nucleating Arp2/3 complex through N-WASP. Nevertheless, these previously identified components are not sufficient to mediate Cdc42-induced actin polymerization in a physiological context. In this paper, we describe the biochemical purification of Toca-1 (transducer of Cdc42-dependent actin assembly) as an essential component of the Cdc42 pathway. Toca-1 binds both N-WASP and Cdc42 and is a member of the evolutionarily conserved PCH protein family. Toca-1 promotes actin nucleation by activating the N-WASP-WIP/CR16 complex, the predominant form of N-WASP in cells. Thus, the cooperative actions of two distinct Cdc42 effectors, the N-WASP-WIP complex and Toca-1, are required for Cdc42-induced actin assembly. These findings represent a significantly revised view of Cdc42-signaling and shed light on the pathogenesis of Wiskott-Aldrich syndrome.
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pubmed:grant |
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pubmed:commentsCorrections |
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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/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/CR16 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/FNBP1L protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 4,5-Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/WASL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/WIPF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Waspip protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Wiskott-Aldrich Syndrome Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Xenopus Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/cdc42 GTP-Binding Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0092-8674
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
118
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
203-16
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15260990-Actin Cytoskeleton,
pubmed-meshheading:15260990-Actins,
pubmed-meshheading:15260990-Amino Acid Sequence,
pubmed-meshheading:15260990-Animals,
pubmed-meshheading:15260990-Base Sequence,
pubmed-meshheading:15260990-Carrier Proteins,
pubmed-meshheading:15260990-Cattle,
pubmed-meshheading:15260990-Cytoskeletal Proteins,
pubmed-meshheading:15260990-DNA, Complementary,
pubmed-meshheading:15260990-Evolution, Molecular,
pubmed-meshheading:15260990-Humans,
pubmed-meshheading:15260990-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15260990-Macromolecular Substances,
pubmed-meshheading:15260990-Molecular Sequence Data,
pubmed-meshheading:15260990-Nerve Tissue Proteins,
pubmed-meshheading:15260990-Phosphatidylinositol 4,5-Diphosphate,
pubmed-meshheading:15260990-Phosphoproteins,
pubmed-meshheading:15260990-Phylogeny,
pubmed-meshheading:15260990-Protein Binding,
pubmed-meshheading:15260990-Signal Transduction,
pubmed-meshheading:15260990-Wiskott-Aldrich Syndrome,
pubmed-meshheading:15260990-Wiskott-Aldrich Syndrome Protein, Neuronal,
pubmed-meshheading:15260990-Xenopus Proteins,
pubmed-meshheading:15260990-cdc42 GTP-Binding Protein
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pubmed:year |
2004
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pubmed:articleTitle |
Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex.
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pubmed:affiliation |
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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