PathwayStep6556 PathwayStep6555 PathwayStep6554 PathwayStep6553 PathwayStep6552 PathwayStep6551 PathwayStep6550 PathwayStep6548 PathwayStep6549 PathwayStep6547 TAK1 Associated with the CBM Complex Phosphorylates IKKbeta Phosphorylation of CARMA1 in B Cells Activation of Protein Kinase C beta (PKC-beta) CARMA1:BCL10:MALT1 Complex Recruits TAK1 and IKK Formation of CBM Complex SCF with beta-TrCP1 or beta-TrCP2 Binds NF-kappaB;phospho-IkB Phosphorylation of I-kappaB by Activated IKK (B cell) Degradation of Ubiquitinated IkB (B cell) Ubiquitination of IkB by SCF-beta-TrCP Translocation of NF-kappaB from the Cytosol to the Nucleus Activation of NF-kappaB in B Cells Authored: May, B, 2011-01-03 DAG and calcium activate protein kinase C beta (PKC-beta, Kochs et al. 1991) which phosphorylates CARMA1 and other proteins (Sommer et al. 2005). Phosphorylated CARMA1 recruits BCL10 and MALT1 to form the CBM complex (Sommer et al. 2005, Tanner et al. 2007) which, in turn, recruits the kinase TAK1 and the IKK complex (Sommer et al. 2005, Shinohara et al. 2005 using chicken cells). TAK1 phosphorylates the IKK-beta subunit, activating it (Wang et al. 2001). The IKK complex then phosphorylates IkB complexed with NF-kappaB dimers in the cytosol (Zandi et al. 1998, Burke et al. 1999, Heilker et al. 1999), resulting in the degradation of IkB (Miyamoto et al. 1994, Traenckner et al. 1994, Alkalay et al. 1995, DiDonato et al. 1995, Li et al. 1995, Lin et al. 1995, Scherer et al. 1995, Chen et al. 1995). NF-kappaB dimers are thereby released and are translocated to the nucleus where they activate transcription (Baeuerle and Baltimore 1988, Blank et al. 1991, Ghosh et al. 2008, Fagerlund et al. 2008). Edited: May, B, 2011-01-03 Pubmed10593898 Pubmed11460167 Pubmed16301747 Pubmed16356855 Pubmed17428801 Pubmed1756723 Pubmed18462924 Pubmed19066035 Pubmed3129195 Pubmed7479848 Pubmed7479976 Pubmed7575604 Pubmed7628694 Pubmed7809113 Pubmed7831327 Pubmed7862124 Pubmed7957109 Pubmed8387275 Pubmed9721103 Pubmed9914500 Reactome Database ID Release 431169091 Reactome, http://www.reactome.org ReactomeREACT_118656 Reviewed: Wienands, J, 2012-02-11