title: Wasp recruitment to the T cell:APC contact site occurs independently of Cdc42 activation.
abstract: Cdc42 and WASP are critical regulators of actin polymerization whose function during T cell signaling is poorly understood. Using a novel reagent that specifically detects Cdc42-GTP in fixed cells, we found that activated Cdc42 localizes to the T cell:APC contact site in an antigen-dependent manner. TCR signaling alone was sufficient to induce localization of Cdc42-GTP, and functional Lck and Zap-70 kinases were required. WASP also localized to the T cell:APC contact site in an antigen-dependent manner. Surprisingly, WASP localization was independent of the Cdc42 binding domain but required the proline-rich domain. Our results indicate that localized WASP activation requires the integration of multiple signals: WASP is recruited via interaction with SH3 domain-containing proteins and is activated by Cdc42-GTP concentrated at the same site.
authors.affiliation: Department of Pathology, University of Chicago, IL 60637, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Cannon
authors.forename: C M
authors.initials: CM
authors.lastname: Labno
authors.forename: G
authors.initials: G
authors.lastname: Bosco
authors.forename: A
authors.initials: A
authors.lastname: Seth
authors.forename: M H
authors.initials: MH
authors.lastname: McGavin
authors.forename: K A
authors.initials: KA
authors.lastname: Siminovitch
authors.forename: M K
authors.initials: MK
authors.lastname: Rosen
authors.forename: J K
authors.initials: JK
authors.lastname: Burkhardt
mesh_terms: D000938:Antigen-Presenting Cells / Q000378:metabolism*; D002451:Cell Compartmentation; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008954:Models, Biological; D011392:Proline; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein; D051746:ZAP-70 Protein-Tyrosine Kinase; D020764:cdc42 GTP-Binding Protein / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D011506:Proteins; D011948:Receptors, Antigen, T-Cell; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D011392:Proline; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D020764:cdc42 GTP-Binding Protein