title: Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization.
abstract: The Rho family of GTPases control diverse biological processes, including cell morphology and mitogenesis. We have identified WASP, the protein that is defective in Wiskott-Aldrich syndrome (WAS), as a novel effector for CDC42Hs, but not for the other Rho family members, Rac and Rho. This interaction is dependent on the presence of the G protein-binding domain. Cellular expression of epitope-tagged WASP produces clusters of WASP that are highly enriched in polymerized actin. This clustering is not observed with a C-terminally deleted WASP and is inhibited by coexpression with dominant negative CDC42Hs-N17, but not with dominant negative forms of Rac or Rho. Thus, WASP provides a novel link between CDC42Hs and the actin cytoskeleton, which suggests a molecular mechanism for many of the cellular abnormalities in WAS. The WASP sequence contains two novel domains that are homologous to other proteins involved in action organization.
authors.affiliation: Onyx Pharmaceuticals, Richmond, California 94806, USA.
authors.forename: M
authors.initials: M
authors.lastname: Symons
authors.forename: J M
authors.initials: JM
authors.lastname: Derry
authors.forename: B
authors.initials: B
authors.lastname: Karlak
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.forename: V
authors.initials: V
authors.lastname: Lemahieu
authors.forename: F
authors.initials: F
authors.lastname: Mccormick
authors.forename: U
authors.initials: U
authors.lastname: Francke
authors.forename: A
authors.initials: A
authors.lastname: Abo
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D016384:Consensus Sequence; D003600:Cytosol / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016324:Sequence Tagged Sites; D014162:Transfection; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein; D020764:cdc42 GTP-Binding Protein
chemical_list: D000199:Actins; D018797:Cell Cycle Proteins; D011506:Proteins; D011994:Recombinant Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein