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Hematopoietic progenitor kinase 1 negatively regulates T cell receptor signaling and T cell-mediated immune responses.

HPK1 is a Ste20-related serine-threonine kinase that inducibly associates with the adaptors SLP-76 and Gads after T cell receptor (TCR) signaling. Here, HPK1 deficiency resulted in enhanced TCR-induced phosphorylation of SLP-76, phospholipase C-gamma1 and the kinase Erk, more-persistent calcium flux, and increased production of cytokines and antigen-specific antibodies. Furthermore, HPK1-deficient mice were more susceptible to experimental autoimmune encephalomyelitis. Although the interaction between SLP-76 and Gads was unaffected, the inducible association of SLP-76 with 14-3-3tau (a phosphorylated serine-binding protein and negative regulator of TCR signaling) was reduced in HPK1-deficient T cells after TCR stimulation. HPK1 phosphorylated SLP-76 and induced the interaction of SLP-76 with 14-3-3tau. Our results indicate that HPK1 negatively regulates TCR signaling and T cell-mediated immune responses.

Pubmed ID: 17115060


  • Shui JW
  • Boomer JS
  • Han J
  • Xu J
  • Dement GA
  • Zhou G
  • Tan TH


Nature immunology

Publication Data

January 20, 2007

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01-AI066895
  • Agency: NIAID NIH HHS, Id: R01-AI42532
  • Agency: NCI NIH HHS, Id: R01-CA87076
  • Agency: NIAID NIH HHS, Id: T32-AI07495

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cells, Cultured
  • Down-Regulation
  • Immunity, Cellular
  • Mice
  • Mitogen-Activated Protein Kinase 3
  • Phosphoproteins
  • Protein-Serine-Threonine Kinases
  • Receptors, Antigen, T-Cell
  • Signal Transduction
  • T-Lymphocytes