Cutting edge: WIP, a binding partner for Wiskott-Aldrich syndrome protein, cooperates with Vav in the regulation of T cell activation.
Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP), specifically binds to a region of WASp that is frequently mutated in Wiskott-Aldrich syndrome. Due to the similar phenotypes of WASp- and Vav-deficient T cells, and the putative importance of the WIP/WASp complex in mediating normal signals from the TCR, we investigated the role of WIP in regulating NF-AT/AP-1-mediated gene transcription. We show that WIP has the ability to enhance Vav-mediated activation of NF-AT/AP-1 gene transcription. In addition, we provide evidence that the interaction of WIP with WASp is necessary, but not sufficient for the ability of WIP to regulate NF-AT/AP-1 activity. Finally, we have identified a region in WIP required for its regulation of NF-AT/AP-1 activity. Our data suggests that the WIP-WASp interaction is important for NF-AT/AP-1-mediated gene transcription, and that defects seen in the activation of T cells from WAS patients may be due to the inability of these cells to form a functional WIP/WASp-signaling complex.
Savoy
D N
DN
Departments of Pharmacology and Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.
Billadeau
D D
DD
Leibson
P J
PJ
D001704:Biopolymers / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D004357:Drug Synergism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic / Q000276:immunology; D014923:Wiskott-Aldrich Syndrome / Q000276:immunology / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein
D001704:Biopolymers; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C496618:VAV1 protein, human; C495767:WAS protein, human; C109903:WIPF1 protein, human; D051316:Wiskott-Aldrich Syndrome Protein