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Review
. 2013;33(3):219-43.
doi: 10.1615/critrevimmunol.2013007056.

The role of CARMA1 in T cells

Marly I Roche  1 , Ravisankar A Ramadas, Benjamin D Medoff
Affiliations
Review

The role of CARMA1 in T cells

Marly I Roche et al. Crit Rev Immunol. 2013.

Abstract

Caspase recruitment domain-containing membrane-associated guanylate kinase protein-1 (CARMA1), a member of the membrane associated guanylate kinase (MAGUK) family of kinases, is essential for T lymphocyte activation and proliferation via T-cell receptor (TCR) mediated NF-κB activation. Recent studies suggest a broader role for CARMA1 regulating other T-cell functions as well as a role in non-TCR-mediated signaling pathways important for lymphocyte development and functions. In addition, CARMA1 has been shown to be an important component in the pathogenesis of several human diseases. Thus, comprehensively defining its mechanisms of action and regulation could reveal novel therapeutic targets for T-cell-mediated diseases and lymphoproliferative disorders.

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Figures

Figure 1
Figure 1
Scaffold proteins can mediate pathway input to a single output (A) or multiple outputs (B). C) Biphasic relationship of scaffold protein levels to output. Reduced output at high levels of scaffold mediated by sequestration of proteins away from each other.
Figure 2
Figure 2
Proposed model of TCR-mediated activation of CARMA1 via PKCθ in T cells. Phosphorylation (P) of the linker region between the C–C and PDZ domains results in opening up of the CARMA1 protein allowing Bcl10 to bind to the CARD domain. This then initiates further downstream signaling.
Figure 3
Figure 3
Schematic of TCR signaling pathway leading to NF-κB and JNK activation.
See this image and copyright information in PMC

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