| First Author | Huang GN | Year | 2008 |
| Journal | Science | Volume | 319 |
| Issue | 5862 | Pages | 476-81 |
| PubMed ID | 18218901 | Mgi Jnum | J:174501 |
| Mgi Id | MGI:5086111 | Doi | 10.1126/science.1151227 |
| Citation | Huang GN, et al. (2008) NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins. Science 319(5862):476-81 |
| abstractText | 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. |
