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 leukemia/lymphoma. 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-kappaB activation by recruiting two adaptor proteins, Bcl10 and MALT1, 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 CARMA1 regulates Bcl10 and MALT1, leading to activation of NF-kappaB. In addition, the roles of CARMA1, Bcl10, and MALT1 in lymphocyte activation and development will also be discussed.
Lin
Xin
X
Department of Microbiology and Immunology, University at Buffalo, 138 Farber Hall, 3435 Main Street, Buffalo, NY 14214, USA. xinlin@buffalo.edu
Wang
Demin
D
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D020169:Caspases; D006162:Guanylate Cyclase / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000276:immunology / Q000378:metabolism*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D011946:Receptors, Antigen / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D009363:Neoplasm Proteins; D011946:Receptors, Antigen; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D006162:Guanylate Cyclase