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-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.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Shui JW,Boomer JS,Han J,Xu J,Dement GA,Zhou G,Tan THdoi
10.1038/ni1416subject
Has Abstractpub_date
2007-01-01 00:00:00pages
84-91issue
1eissn
1529-2908issn
1529-2916pii
ni1416journal_volume
8pub_type
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