PKC beta regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1.
The B cell antigen receptor (BCR)-mediated activation of IkappaB kinase (IKK) and nuclear factor-kappaB require protein kinase C (PKC)beta; however, the mechanism by which PKCbeta regulates IKK is unclear. Here, we demonstrate that another protein kinase, TGFbeta-activated kinase (TAK)1, is essential for IKK activation in response to BCR stimulation. TAK1 interacts with the phosphorylated CARMA1 (also known as caspase recruitment domain [CARD]11, Bimp3) and this interaction is mediated by PKCbeta. IKK is also recruited to the CARMA1-Bcl10-mucosal-associated lymphoid tissue 1 adaptor complex in a PKCbeta-dependent manner. Hence, our data suggest that phosphorylation of CARMA1, mediated by PKCbeta, brings two key protein kinases, TAK1 and IKK, into close proximity, thereby allowing TAK1 to phosphorylate IKK.
Shinohara
Hisaaki
H
Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
Yasuda
Tomoharu
T
Aiba
Yuichi
Y
Sanjo
Hideki
H
Hamadate
Megumi
M
Watarai
Hiroshi
H
Sakurai
Hiroaki
H
Kurosaki
Tomohiro
T
D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D053468:CARD Signaling Adaptor Proteins; D002460:Cell Line; D002645:Chickens; D006162:Guanylate Cyclase / Q000378:metabolism*; D051550:I-kappa B Kinase / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D064546:Protein Kinase C beta; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D000099151:MAP Kinase Kinase Kinase 7
D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D006162:Guanylate Cyclase; D051550:I-kappa B Kinase; D020930:MAP Kinase Kinase Kinases; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D011947:Receptors, Antigen, B-Cell; D000099151:MAP Kinase Kinase Kinase 7; C426242:CARD11 protein, human