Linked Life Data

11432863

Source:http://linkedlifedata.com/resource/pubmed/id/11432863

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2001-8-27
pubmed:abstractText
Neural Wiskott-Aldrich syndrome protein (N-WASP) is an essential regulator of actin cytoskeleton formation via its association with the actin-related protein (Arp) 2/3 complex. It is believed that the C-terminal Arp2/3 complex-activating domain (verprolin homology, cofilin homology, and acidic (VCA) or C-terminal region of WASP family proteins domain) of N-WASP is usually kept masked (autoinhibition) but is opened upon cooperative binding of upstream regulators such as Cdc42 and phosphatidylinositol 4,5-bisphosphate (PIP2). However, the mechanisms of autoinhibition and association with Arp2/3 complex are still unclear. We focused on the acidic region of N-WASP because it is thought to interact with Arp2/3 complex and may be involved in autoinhibition. Partial deletion of acidic residues from the VCA portion alone greatly reduced actin polymerization activity, demonstrating that the acidic region contributes to Arp2/3 complex-mediated actin polymerization. Surprisingly, the same partial deletion of the acidic region in full-length N-WASP led to constitutive activity comparable with the activity seen with the VCA portion. Therefore, the acidic region in full-length N-WASP plays an indispensable role in the formation of the autoinhibited structure. This mutant contains WASP-homology (WH) 1 domain with weak affinity to the Arp2/3 complex, leading to activity in the absence of part of the acidic region. Furthermore, the actin comet formed by the DeltaWH1 mutant of N-WASP was much smaller than that of wild-type N-WASP. Partial deletion of acidic residues did not affect actin comet size, indicating the importance of the WH1 domain in actin structure formation. Collectively, the acidic region of N-WASP plays an essential role in Arp2/3 complex activation as well as in the formation of the autoinhibited structure, whereas the WH1 domain complements the activation of the Arp2/3 complex achieved through the VCA portion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33175-80
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed-meshheading:11432863-Actin-Related Protein 2, pubmed-meshheading:11432863-Actin-Related Protein 3, pubmed-meshheading:11432863-Actins, pubmed-meshheading:11432863-Amino Acid Sequence, pubmed-meshheading:11432863-Amino Acid Substitution, pubmed-meshheading:11432863-Animals, pubmed-meshheading:11432863-Binding Sites, pubmed-meshheading:11432863-Cytoskeletal Proteins, pubmed-meshheading:11432863-Humans, pubmed-meshheading:11432863-Kinetics, pubmed-meshheading:11432863-Molecular Sequence Data, pubmed-meshheading:11432863-Mutagenesis, Site-Directed, pubmed-meshheading:11432863-Nerve Tissue Proteins, pubmed-meshheading:11432863-Recombinant Proteins, pubmed-meshheading:11432863-Spodoptera, pubmed-meshheading:11432863-Transfection, pubmed-meshheading:11432863-Wiskott-Aldrich Syndrome, pubmed-meshheading:11432863-Wiskott-Aldrich Syndrome Protein, Neuronal
pubmed:year
2001
pubmed:articleTitle
Identification of another actin-related protein (Arp) 2/3 complex binding site in neural Wiskott-Aldrich syndrome protein (N-WASP) that complements actin polymerization induced by the Arp2/3 complex activating (VCA) domain of N-WASP.
pubmed:affiliation
Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 1088639, Japan.
pubmed:publicationType
Journal Article