Cutting edge: WIP, a binding partner for Wiskott-Aldrich syndrome protein, cooperates with Vav in the regulation of T cell activation

J Immunol. 2000 Mar 15;164(6):2866-70. doi: 10.4049/jimmunol.164.6.2866.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biopolymers / physiology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Cycle Proteins*
  • Cytoskeletal Proteins
  • DNA Mutational Analysis
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology
  • Drug Synergism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Jurkat Cells
  • Lymphocyte Activation / immunology*
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Protein Binding / genetics
  • Protein Binding / immunology
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-vav
  • Sequence Deletion
  • T-Lymphocytes / immunology*
  • Transcription Factor AP-1 / metabolism
  • Transcription Factor AP-1 / physiology
  • Transcription Factors / metabolism
  • Transcription Factors / physiology
  • Transcription, Genetic / immunology
  • Wiskott-Aldrich Syndrome / immunology
  • Wiskott-Aldrich Syndrome / metabolism
  • Wiskott-Aldrich Syndrome Protein

Substances

  • Biopolymers
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-vav
  • Transcription Factor AP-1
  • Transcription Factors
  • VAV1 protein, human
  • WAS protein, human
  • WIPF1 protein, human
  • Wiskott-Aldrich Syndrome Protein