Overexpression of the Wiskott-Aldrich syndrome protein N-terminal domain in transgenic mice inhibits T cell proliferative responses via TCR signaling without affecting cytoskeletal rearrangements.

Affecting Cytoskeletal Rearrangements Responses Via TCR Signaling Without Transgenic Mice Inhibits T Cell Proliferative Syndrome Protein N-Terminal Domain in Overexpression of the Wiskott-Aldrich

Identification of Fyn as the binding partner for the WASP N-terminal domain in T cells.

Wiskott-Aldrich syndrome protein (WASP) plays important roles in TCR signaling. In transgenic (Tg) mice, over-expression of the WASP N-terminal region (exons 1-5) including the enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) homology 1 (EVH1) domain and anti-WASP-EVH1 single-chain variable fragment (scFv) intracellular expressed antibodies (intrabodies) impairs IL-2 production in activ...

Single domain intrabodies against WASP inhibit TCR-induced immune responses in transgenic mice T cells

Intrabody technology provides a novel approach to decipher the molecular mechanisms of protein function in cells. Single domains composed of only the variable regions (V(H) or V(L)) of antibodies are the smallest recombinant antibody fragments to be constructed thus far. In this study, we developed transgenic (Tg) mice expressing the V(H) or V(L) single domains derived from a monoclonal antibod...

Antigen Receptor–Induced Activation and Cytoskeletal Rearrangement Are Impaired in Wiskott-Aldrich Syndrome Protein–Deficient Lymphocytes

The Wiskott-Aldrich syndrome protein (WASp) has been implicated in modulation of lymphocyte activation and cytoskeletal reorganization. To address the mechanisms whereby WASp subserves such functions, we have examined WASp roles in lymphocyte development and activation using mice carrying a WAS null allele (WAS(-)(/)(-)). Enumeration of hemopoietic cells in these animals revealed total numbers ...

Critical Roles of the WASP N-Terminal Domain and Btk in LPS-Induced Inflammatory Response in Macrophages

While Wiskott-Aldrich syndrome protein (WASP) plays critical roles in TCR signaling as an adaptor molecule, how it transduces innate immune signals remains to be elucidated. To investigate the roles of WASP in innate immune cells, we established bone marrow-derived macrophage (BMDM) cell lines from WASP15 transgenic (Tg) mice overexpressing the WASP N-terminal region (exons 1-5). Upon LPS stimu...