NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins |
| |
Authors: | Huang Guo N Huso David L Bouyain Samuel Tu Jianchen McCorkell Kelly A May Michael J Zhu Yuwen Lutz Michael Collins Samuel Dehoff Marlin Kang Shin Whartenby Katharine Powell Jonathan Leahy Daniel Worley Paul F |
| |
Affiliation: | Program in Biochemistry, Cellular and Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. |
| |
Abstract: | T cell receptor (TCR) and costimulatory receptor (CD28) signals cooperate in activating T cells, although understanding of how these pathways are themselves regulated is incomplete. We found that Homer2 and Homer3, members of the Homer family of cytoplasmic scaffolding proteins, are negative regulators of T cell activation. This is achieved through binding of nuclear factor of activated T cells (NFAT) and by competing with calcineurin. Homer-NFAT binding was also antagonized by active serine-threonine kinase AKT, thereby enhancing TCR signaling via calcineurin-dependent dephosphorylation of NFAT. This corresponded with changes in cytokine expression and an increase in effector-memory T cell populations in Homer-deficient mice, which also developed autoimmune-like pathology. These results demonstrate a further means by which costimulatory signals are regulated to control self-reactivity. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|