Negative feedback loop in T-cell activation through MAPK-catalyzed threonine phosphorylation of LAT.
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.
Matsuda
Satoshi
S
Department of Microbiology and Immunology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
Miwa
Yoshihiro
Y
Hirata
Yasuko
Y
Minowa
Akiko
A
Tanaka
Junko
J
Nishida
Eisuke
E
Koyasu
Shigeo
S
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002384:Catalysis; D025461:Feedback, Physiological; D006801:Humans; D019169:Jurkat Cells; D008156:Luciferases / Q000378:metabolism; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013912:Threonine / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D010738:Type C Phospholipases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D013912:Threonine; D008156:Luciferases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium