Phosphorylation of CARMA1 plays a critical role in T Cell receptor-mediated NF-kappaB activation. Immunity 2005 Dec;23(6):575-85
Date
12/17/2005Pubmed ID
16356856DOI
10.1016/j.immuni.2005.10.007Scopus ID
2-s2.0-28844499919 (requires institutional sign-in at Scopus site) 239 CitationsAbstract
CARMA1 mediates T cell receptor (TCR)-induced NF-kappaB activation. However, how TCR links to CARMA1 in the signaling pathway is not clear. Here, we show that CARMA1 is inducibly phosphorylated after TCR-CD28 costimulation. This phosphorylation is likely induced by PKCtheta, since PKCtheta induces phosphorylation of CARMA1 in vitro and in vivo. Our results indicate that the PKCtheta-induced phosphorylation of CARMA1 likely occurs on Ser552 on the Linker region of CARMA1. Importantly, expression of CARMA1 mutant, in which Ser552 is mutated, fails to mediate TCR-induced NF-kappaB activation in CARMA1-deficient T cells. The functional defect of this CARMA1 mutant is likely due to the fact that this mutant cannot be phosphorylated at the critical residue, thereby failing to recruit the downstream signaling components into the immunological synapse. Together, our studies provide the first genetic evidence that the phosphorylation of CARMA1 plays a critical role in the TCR signaling pathway.
Author List
Matsumoto R, Wang D, Blonska M, Li H, Kobayashi M, Pappu B, Chen Y, Wang D, Lin XAuthor
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Apoptosis Regulatory Proteins
CARD Signaling Adaptor Proteins
CD28 Antigens
Cell Line
Electrophoresis, Polyacrylamide Gel
Gene Components
Guanylate Kinases
Humans
Immunity, Cellular
Luciferases
Mass Spectrometry
Membrane Microdomains
Mice
Molecular Sequence Data
Mutation
NF-kappa B
Phosphorylation
Protein Kinase C
Receptors, Antigen, T-Cell
Sequence Alignment
Sequence Analysis, DNA
Signal Transduction
Transcriptional Activation
