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NF‐ĸB activation pathways induced by T cell costimulation
Author(s) -
Schmitz M. Lienhard,
Bacher Susanne,
Dienz Oliver
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-1100rev
Subject(s) - microbiology and biotechnology , signal transducing adaptor protein , diacylglycerol kinase , signal transduction , biology , phosphorylation , protein kinase c , iκb kinase , pleckstrin homology domain , nf κb
Analysis of knockout mice and of T cells deficient for individual signaling proteins allowed the identification of novel members of the costimulation‐ induced NF‐ĸB activation pathway while biochemical approaches started to unveil their functional mecha‐ nisms. These results show that NF‐ĸB activation de‐ pends on an early wave of tyrosine phosphorylation that allows the inducible formation of multiprotein com‐ plexes containing several proteins required for NF‐ĸB activation: adaptor proteins including Src homology 2 domain‐containing leukocyte phosphoprotein 76 (SLP‐76) and proteins with enzymatic activity, such as phos‐ pholipase C (PLC) γ and the exchange factor Vav1. While Vav1 contributes to Rac‐dependent reorganization of the actin cytoskeleton, activated PLC γ 1 gener‐ ates the protein kinase C (PKC) activator diacylglycerol. In T cells, the novel PKC isoform PKCθ is indispens‐ able for NF‐ĸB activation and its enzymatic activity depends on recruitment to the immunological synapse. Downstream from PKCθ, the caspase recruitment do‐ main (CARD) proteins CARD11/CARMA1 and Bcl10 relay T cell receptor‐derived signals to the IĸB kinase (IKK) complex. Many members of the NF‐ĸB activation cascade, including the IKKs, are either constitutively or inducibly translocated to the lipid raft fraction, showing a highly organized spatial distribution of these NF‐ĸB activating proteins.—Schmitz, M. L., Bacher, S., Dienz, O. NF‐ĸB activation pathways induced by T cell co‐ stimulation. FASEB J. 17, 2187‐2193 (2003)