Article abstract
Nature Immunology 8, 84 - 91 (2006)
Published online: 19 November 2006 | doi:10.1038/ni1416
Hematopoietic progenitor kinase 1 negatively regulates T cell receptor signaling and T cell–mediated immune responses
Jr-Wen Shui1, Jonathan S Boomer1, Jin Han1, Jun Xu1, Gregory A Dement1, Guisheng Zhou1 & Tse-Hua Tan1
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-
1 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 14-3-3
(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 14-3-3. Our results indicate that HPK1 negatively regulates TCR signaling and T cell–mediated immune responses.
- Department of Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Correspondence to: Tse-Hua Tan1 e-mail: ttan@bcm.edu
