Ca2+/calmodulin-dependent Protein Kinase II is a Modulator of CARMA1-mediated NF-kappaB Activation

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2006 Jul 1

PMID 16809782

Citations 54

Authors

Kazuhiro Ishiguro

Todd Green

Joseph Rapley

Heather Wachtel

Cosmas Giallourakis

Aimee Landry

Zhifang Cao

Naifang Lu

Ando Takafumi

Hidemi Goto

Mark J Daly

Ramnik J Xavier

Affiliations

Soon will be listed here.

Abstract

CARMA1 is a central regulator of NF-kappaB activation in lymphocytes. CARMA1 and Bcl10 functionally interact and control NF-kappaB signaling downstream of the T-cell receptor (TCR). Computational analysis of expression neighborhoods of CARMA1-Bcl10MALT 1 for enrichment in kinases identified calmodulin-dependent protein kinase II (CaMKII) as an important component of this pathway. Here we report that Ca(2+)/CaMKII is redistributed to the immune synapse following T-cell activation and that CaMKII is critical for NF-kappaB activation induced by TCR stimulation. Furthermore, CaMKII enhances CARMA1-induced NF-kappaB activation. Moreover, we have shown that CaMKII phosphorylates CARMA1 on Ser109 and that the phosphorylation facilitates the interaction between CARMA1 and Bcl10. These results provide a novel function for CaMKII in TCR signaling and CARMA1-induced NF-kappaB activation.

Citing Articles

The Influence of Symbiont Identity on the Proteomic and Metabolomic Responses of the Model Cnidarian Aiptasia to Thermal Stress.

Lust B, Matthews J, Oakley C, Lewis R, Mendis H, Peng L Environ Microbiol. 2025; 27(3):e70073.

PMID: 40056008 PMC: 11889536. DOI: 10.1111/1462-2920.70073.

WNT11 Promotes immune evasion and resistance to Anti-PD-1 therapy in liver metastasis.

Jiang W, Guan B, Sun H, Mi Y, Cai S, Wan R Nat Commun. 2025; 16(1):1429.

PMID: 39920102 PMC: 11806061. DOI: 10.1038/s41467-025-56714-z.

Molecular Mechanisms of Alzheimer's Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy.

Ahn E, Park J Cells. 2025; 14(2).

PMID: 39851517 PMC: 11764136. DOI: 10.3390/cells14020089.

Cellular and molecular imaging of CAR-T cell-based immunotherapy.

Liu L, Yoon C, Yuan Z, Guo T, Qu Y, He P Adv Drug Deliv Rev. 2023; 203:115135.

PMID: 37931847 PMC: 11052581. DOI: 10.1016/j.addr.2023.115135.

A hepatokine derived from the ER protein CREBH promotes triglyceride metabolism by stimulating lipoprotein lipase activity.

Kim H, Song Z, Zhang R, Davies B, Zhang K Sci Signal. 2023; 16(768):eadd6702.

PMID: 36649378 PMC: 10080946. DOI: 10.1126/scisignal.add6702.

References

Sun L, Deng L, Ea C, Xia Z, Chen Z . The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol Cell. 2004; 14(3):289-301. DOI: 10.1016/s1097-2765(04)00236-9. View

Weil R, Israel A . Deciphering the pathway from the TCR to NF-kappaB. Cell Death Differ. 2006; 13(5):826-33. DOI: 10.1038/sj.cdd.4401856. View

Caenepeel S, Charydczak G, Sudarsanam S, Hunter T, Manning G . The mouse kinome: discovery and comparative genomics of all mouse protein kinases. Proc Natl Acad Sci U S A. 2004; 101(32):11707-12. PMC: 511041. DOI: 10.1073/pnas.0306880101. View

Andersson L, Porath J . Isolation of phosphoproteins by immobilized metal (Fe3+) affinity chromatography. Anal Biochem. 1986; 154(1):250-4. DOI: 10.1016/0003-2697(86)90523-3. View

Bui J, Calbo S, Kane L, Gardner P, Hedrick S . A role for CaMKII in T cell memory. Cell. 2000; 100(4):457-67. DOI: 10.1016/s0092-8674(00)80681-9. View

Uren A, ORourke K, Aravind L, Pisabarro M, Seshagiri S, Koonin E . Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell. 2000; 6(4):961-7. DOI: 10.1016/s1097-2765(00)00094-0. View

Ruland J, Duncan G, Elia A, del Barco Barrantes I, Nguyen L, Plyte S . Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure. Cell. 2001; 104(1):33-42. DOI: 10.1016/s0092-8674(01)00189-1. View

Dustin M, Cooper J . The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling. Nat Immunol. 2001; 1(1):23-9. DOI: 10.1038/76877. View

Bertin J, Wang L, Guo Y, Jacobson M, Poyet J, Srinivasula S . CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B. J Biol Chem. 2001; 276(15):11877-82. DOI: 10.1074/jbc.M010512200. View

10.

Lucas P, Yonezumi M, Inohara N, McAllister-Lucas L, Abazeed M, Chen F . Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. J Biol Chem. 2001; 276(22):19012-9. DOI: 10.1074/jbc.M009984200. View

11.

Jang M, Goo Y, Sohn Y, Kim Y, Lee S, Kang H . Ca2+/calmodulin-dependent protein kinase IV stimulates nuclear factor-kappa B transactivation via phosphorylation of the p65 subunit. J Biol Chem. 2001; 276(23):20005-10. DOI: 10.1074/jbc.M010211200. View

12.

Hughes K, Edin S, Antonsson A, Grundstrom T . Calmodulin-dependent kinase II mediates T cell receptor/CD3- and phorbol ester-induced activation of IkappaB kinase. J Biol Chem. 2001; 276(38):36008-13. DOI: 10.1074/jbc.M106125200. View

13.

Parrish S, Fleenor J, Xu S, Mello C, Fire A . Functional anatomy of a dsRNA trigger: differential requirement for the two trigger strands in RNA interference. Mol Cell. 2000; 6(5):1077-87. DOI: 10.1016/s1097-2765(00)00106-4. View

14.

Hudmon A, Schulman H . Neuronal CA2+/calmodulin-dependent protein kinase II: the role of structure and autoregulation in cellular function. Annu Rev Biochem. 2002; 71:473-510. DOI: 10.1146/annurev.biochem.71.110601.135410. View

15.

Sancho D, Montoya M, Monjas A, Gordon-Alonso M, Katagiri T, Gil D . TCR engagement induces proline-rich tyrosine kinase-2 (Pyk2) translocation to the T cell-APC interface independently of Pyk2 activity and in an immunoreceptor tyrosine-based activation motif-mediated fashion. J Immunol. 2002; 169(1):292-300. DOI: 10.4049/jimmunol.169.1.292. View

16.

Wang D, You Y, Case S, McAllister-Lucas L, Wang L, DiStefano P . A requirement for CARMA1 in TCR-induced NF-kappa B activation. Nat Immunol. 2002; 3(9):830-5. DOI: 10.1038/ni824. View

17.

Gaide O, Favier B, Legler D, Bonnet D, Brissoni B, Valitutti S . CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation. Nat Immunol. 2002; 3(9):836-43. DOI: 10.1038/ni830. View

18.

Pomerantz J, Denny E, Baltimore D . CARD11 mediates factor-specific activation of NF-kappaB by the T cell receptor complex. EMBO J. 2002; 21(19):5184-94. PMC: 129028. DOI: 10.1093/emboj/cdf505. View

19.

McManus M, Haines B, Dillon C, Whitehurst C, Van Parijs L, Chen J . Small interfering RNA-mediated gene silencing in T lymphocytes. J Immunol. 2002; 169(10):5754-60. DOI: 10.4049/jimmunol.169.10.5754. View

20.

Manning G, Whyte D, Martinez R, Hunter T, Sudarsanam S . The protein kinase complement of the human genome. Science. 2002; 298(5600):1912-34. DOI: 10.1126/science.1075762. View