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First published online December 1, 2003
doi: 10.1242/10.1242/jcs.00904

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NF-B signaling in lymphocytes: a new cast of characters

¹ Department of Pathology, University of Michigan Medical School, 4131 CCGC, 1500 East Medical Center Dr., Ann Arbor, MI 48109, USA
² Department of Pediatrics, University of Michigan Medical School, 4131 CCGC, 1500 East Medical Center Dr., Ann Arbor, MI 48109, USA

View larger version (45K): [in a new window]   Fig. 1. Proximal signaling factors recruited to the SMAC. Several receptor-associated tyrosine kinases and adaptor proteins are recruited to the SMAC upon engagement of the antigen receptor complex. Key players are represented here. DAG is also generated through the action of PLC1 and subsequently serves to activate PKC, which is the isoform of PKC that is specifically recruited to the SMAC in T cells.

View larger version (51K): [in a new window]   Fig. 2. Chromosomal translocations in MALT lymphoma. Shown are the products of two recurrent chromosomal translocations seen in MALT B-cell lymphomas. Overexpression of either wild-type Bcl10 or the API2-MALT1 fusion protein is thought to result in excessive NF-B activation, although Bcl10 might require an intact downstream factor, MALT1. In both cases, oligomerization-dependent activation of the MALT1 protease (caspase-like) domain appears to play an important role for the subsequent stimulation of the IKK complex.

View larger version (37K): [in a new window]   Fig. 3. MAGUK subfamily classification. All MAGUKs are defined by the presence of at least one PDZ, SH3 and GUK-like domain. The various subfamilies are distinguished by the presence of additional domains (e.g. the CARD and coiled-coil domains of the Bimp subfamily), or by unique linear arrangements of the key domains.

View larger version (59K): [in a new window]   Fig. 4. Downstream events in the TCR-mediated activation of NF-B. Recent studies have implicated several new players in the activation of NF-B, including CARMA1, Bcl10 and MALT1. However, as indicated in the text, numerous unanswered questions remain.