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Hematopoietic progenitor kinase 1 negatively regulates T cell receptor signaling and T cell–mediated immune responses.
- Source :
- Nature Immunology; Jan2007, Vol. 8 Issue 1, p84-91, 8p
- Publication Year :
- 2007
-
Abstract
- 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-γ1 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 14-3-3τ (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 14-3-3τ. Our results indicate that HPK1 negatively regulates TCR signaling and T cell–mediated immune responses. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15292908
- Volume :
- 8
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 23462641
- Full Text :
- https://doi.org/10.1038/ni1416