Meta-Biol

• Pathways

CARMA1 (CARD11/Caspase recruitment domain-containing protein 11), BCL10 (B-cell lymphoma/leukemia 10) and MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1)/paracaspase have been identified as signaling components that act downstream of PKC-theta. CARMA1 is a scaffold protein and recruits BCL10, MALT1, PKC and TRAF6 to form a multi protein complex. CARMA1 exists in an inactive conformation in which the linker region binds to and blocks the accessibility of the CARD motif. Upon stimulation S552 and S645 linker residues are phosphorylated by PKC-theta and this may weaken this interaction, inducing an open conformation of CARMA1. Further phosphorylation studies have revealed other phosphorylation sites (S109, S551 and S555) that may also promote activation of CARMA1. Serene/threonine kinases PKC-beta, IKKbeta, HPK1 and CaMKII are involved in triggering CARMA1 activation (Thome et al. 2010, Rueda & Thome 2005). (only phosphorylated S552 and S645 are represented in this reaction)