Phosphorylation of the CARMA1 linker controls NF-κB activation

Karen Sommer, Beichu Guo, Joel L Pomerantz, Ashok D. Bandaranayake, Miguel E. Moreno-García, Yulia L. Ovechkina, David J. Rawlings

Research output: Contribution to journalArticle

Abstract

PKC isoforms and CARMA1 play crucial roles in immunoreceptor-dependent NF-κB activation. We tested whether PKC-dependent phosphorylation of CARMA1 directly regulates this signaling cascade. B cell antigen receptor (BCR) engagement led to the progressive recruitment of CARMA1 into lipid rafts and to the association of CARMA1 with, and phosphorylation by, PKCβ. Furthermore, PKCβ interacted with the serine-rich CARMA1 linker, and both PKCβ and PKCθ phosphorylated identical serine residues (S564, S649, and S657) within this linker. Mutation of two of these sites ablated the functional activity of CARMA1. In contrast, deletion of the linker resulted in constitutive, receptor- and PKC-independent NF-κB activation. Together, our data support a model whereby CARMA1 phosphorylation controls NF-κB activation by triggering a shift from an inactive to an active CARMA1 conformer. This PKC-dependent switch regulates accessibility of the CARD and CC domains and controls assembly and full activation of the membrane-associated IκB kinase (IKK) signalosome.

Original languageEnglish (US)
Pages (from-to)561-574
Number of pages14
JournalImmunity
Volume23
Issue number6
DOIs
StatePublished - Dec 2005

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Phosphorylation
S 657
Serine
B-Cell Antigen Receptors
Protein Isoforms
Phosphotransferases
Lipids
Mutation
Membranes
Caspase Activation and Recruitment Domain

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Sommer, K., Guo, B., Pomerantz, J. L., Bandaranayake, A. D., Moreno-García, M. E., Ovechkina, Y. L., & Rawlings, D. J. (2005). Phosphorylation of the CARMA1 linker controls NF-κB activation. Immunity, 23(6), 561-574. https://doi.org/10.1016/j.immuni.2005.09.014

Phosphorylation of the CARMA1 linker controls NF-κB activation. / Sommer, Karen; Guo, Beichu; Pomerantz, Joel L; Bandaranayake, Ashok D.; Moreno-García, Miguel E.; Ovechkina, Yulia L.; Rawlings, David J.

In: Immunity, Vol. 23, No. 6, 12.2005, p. 561-574.

Research output: Contribution to journalArticle

Sommer, K, Guo, B, Pomerantz, JL, Bandaranayake, AD, Moreno-García, ME, Ovechkina, YL & Rawlings, DJ 2005, 'Phosphorylation of the CARMA1 linker controls NF-κB activation', Immunity, vol. 23, no. 6, pp. 561-574. https://doi.org/10.1016/j.immuni.2005.09.014
Sommer K, Guo B, Pomerantz JL, Bandaranayake AD, Moreno-García ME, Ovechkina YL et al. Phosphorylation of the CARMA1 linker controls NF-κB activation. Immunity. 2005 Dec;23(6):561-574. https://doi.org/10.1016/j.immuni.2005.09.014
Sommer, Karen ; Guo, Beichu ; Pomerantz, Joel L ; Bandaranayake, Ashok D. ; Moreno-García, Miguel E. ; Ovechkina, Yulia L. ; Rawlings, David J. / Phosphorylation of the CARMA1 linker controls NF-κB activation. In: Immunity. 2005 ; Vol. 23, No. 6. pp. 561-574.
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