Negative feedback loop in T-cell activation through MAPK-catalyzed threonine phosphorylation of LAT |
| |
Authors: | Matsuda Satoshi Miwa Yoshihiro Hirata Yasuko Minowa Akiko Tanaka Junko Nishida Eisuke Koyasu Shigeo |
| |
Affiliation: | Department of Microbiology and Immunology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan. |
| |
Abstract: | Mitogen-activated protein kinase (MAPK) cascades are involved in a variety of cellular responses including proliferation, differentiation, and apoptosis. We have developed an expression screening method to detect in vivo substrates of MAPKs in mammalian cells, and identified a membrane protein, linker for activation of T cells (LAT), as an MAPK target. LAT, an adapter protein essential for T-cell signaling, is phosphorylated at its Thr 155 by ERK in response to T-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of LAT to recruit PLCgamma1 and SLP76, leading to attenuation of subsequent downstream events such as [Ca2+]i mobilization and activation of the ERK pathway. Our data reveal a new role for MAPKs in a negative feedback loop in T-cell activation via threonine phosphorylation of LAT. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|