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Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42.

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder with the most severe pathology in the T lymphocytes and platelets. The disease arises from mutations in the gene encoding the WAS protein. T lymphocytes of affected males with WAS exhibit a severe disturbance of the actin cytoskeleton, suggesting that the WAS protein could regulate its organization. We show here that WAS protein interacts with a member of the Rho family of GTPases, Cdc42. This interaction, which is guanosine 5'-triphosphate (GTP)-dependent, was detected in cell lysates, in transient transfections and with purified recombinant proteins. A weaker interaction was also detected with Rac1 using WAS protein from cell lysates. It was also found that different mutant WAS proteins from three affected males retained their ability to interact with Cdc42 and that the level of expression of the WAS protein in these mutants was only 2-5% of normal. Taken together these data suggest that the WAS protein might function as a signal transduction adaptor downstream of Cdc42, and in affected males, the cytoskeletal abnormalities may result from a defect in Cdc42 signaling.

Pubmed ID: 8643625

Authors

  • Kolluri R
  • Tolias KF
  • Carpenter CL
  • Rosen FS
  • Kirchhausen T

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

May 28, 1996

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Cycle Proteins
  • Cell Line
  • Cercopithecus aethiops
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Peptides
  • Proteins
  • Recombinant Fusion Proteins
  • Reference Values
  • T-Lymphocytes
  • Transfection
  • Wiskott-Aldrich Syndrome
  • Wiskott-Aldrich Syndrome Protein
  • cdc42 GTP-Binding Protein, Saccharomyces cerevisiae