title: TCR signaling to NF-κB and mTORC1: Expanding roles of the CARMA1 complex.
abstract: Naïve T-cell activation requires signals from both the T-cell receptor (TCR) and the costimulatory molecule CD28. A central mediator of the TCR and CD28 signals is the scaffold protein CARMA1, which functions by forming a complex with partner proteins, Bcl10 and MALT1. A well-known function of the CARMA1 signaling complex is to mediate activation of IκB kinase (IKK) and its target transcription factor NF-κB, thereby promoting T-cell activation and survival. Recent evidence suggests that CARMA1 also mediates TCR/CD28-stimulated activation of the IKK-related kinase TBK1, which plays a role in regulating the homeostasis and migration of T cells. Moreover, the CARMA1 complex connects the TCR/CD28 signals to the activation of mTORC1, a metabolic kinase regulating various aspects of T-cell functions. This review will discuss the mechanism underlying the activation of the CARMA1-dependent signaling pathways and their roles in regulating T-cell functions.
authors.affiliation: Central Laboratory, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding 071000, China.
authors.forename: Jian-hong
authors.initials: JH
authors.lastname: Shi
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. Electronic address: ssun@mdanderson.org.
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000276:immunology* / Q000378:metabolism; D006162:Guanylate Cyclase / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases / Q000276:immunology* / Q000378:metabolism
chemical_list: D053468:CARD Signaling Adaptor Proteins; D046912:Multiprotein Complexes; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; C426242:CARD11 protein, human; D006162:Guanylate Cyclase
keywords: CARMA1; Glutamine; NF-κB; T-cell activation; T-cell tolerance; TCR signaling; mTORC1