J Exp Med. 2007 Dec 24;204(13):3285-93. Epub 2007 Dec 17.

IkappaB kinase beta-induced phosphorylation of CARMA1 contributes to CARMA1 Bcl10 MALT1 complex formation in B cells.External

Shinohara, H., Maeda, S., Watarai, H., Kurosaki, T.,
--- - Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Protein kinase C (PKC) beta has been reported (Shinohara, H., T. Yasuda, Y. Aiba, H. Sanjo, M. Hamadate, H. Watarai, H. Sakurai, and T. Kurosaki. 2005. J. Exp. Med. 202:1423-1431; Sommer, K., B. Guo, J.L. Pomerantz, A.D. Bandaranayake, M.E. Moreno-Garcia, Y.L. Ovechkina, and D.J. Rawlings. 2005. Immunity. 23:561-574) to play a crucial role in B cell receptor (BCR)-mediated IkappaB kinase (IKK) activation through phosphorylation of caspase recruitment domain 11, Bimp3 (CARMA1). However, it remains unclear whether this PKCbeta-mediated phosphorylation accounts fully for the activation status of CARMA1, because involvement of other kinases, such as phosphoinositide 3-kinase-dependent kinase 1, has also been suggested. We show that PKCbeta mediates phosphorylation of CARMA1 on Ser668, which in turn is essential for BCR-mediated CARMA1-Bcl10-mucosal-associated lymphoid tissue 1 (MALT1) association and subsequent IKK activation. Our analyses also demonstrate that the downstream kinase IKKbeta contributes to facilitating formation of the complex CARMA1-Bcl10-MALT1 by mediating phosphorylation of CARMA1. Hence, our data suggest that PKCbeta is crucial for initial activation of IKK. The activated IKKbeta does not merely function as an effector enzyme but also modifies the upstream signaling complex through a feedback mechanism, thereby optimizing the strength and duration of the nuclear factor kappaB signal.
PMID: 18086859External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD Bcl-10 Link CARD11 Co-immunoprecipitation DT40 Not used Not specified Not specified 18086859
(Link: click this icon to show interactions only between the two corresponding DDs)