The roles of CARMA1, Bcl10, and MALT1 in antigen receptor signaling

Lymphocyte activation plays a critical role in immune responses. Dysregulation of lymphocyte activation can cause autoimmune, immunodeficient diseases, or leukemiaAymphoma. Lymphocyte activation is triggered by stimulation of antigen receptors, T cell receptors (TCR) or B cell receptors (BCR), on the surfaces of T or B lymphocyte, respectively. Stimulation of TCR or BCR induces a series of signal transduction cascades leading to activation of multiple transcription factors including NF-kappaB. Recent studies demonstrate that CARMA1, a scaffold protein, plays an essential role in mediating TCR- or BCR-induced NF-KB activation by recruiting two adaptor proteins, Bel 10 and MALT 1, to lipid rafts following stimulation of antigen receptors. In this review, we will discuss the mechanism by which proximal signaling components connect antigen receptor signaling to CARMA1, and how CARMA 1 regulates Bel 10 and MALT 1, leading to activation of NF-kappaB. In addition, the roles of CARMA1, Bcl10, and MALT 1 in lymphocyte activation and development will also be discussed. (C) 2004 Elsevier Ltd. All rights reserved.