Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Hiromitsu HaraEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_297


Historical Background

The mucosa associated lymphoid tissue lymphoma (MALTL)-associated molecules, B-cell lymphoma 10 (BCL10) and MALTL translocation gene 1 (MALT1), form a complex and play an essential role in nuclear factor κB (NF-κB) activation through immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors and some G-protein-coupled receptors (Hara and Saito 2009). CARMA1 is a member of CARD-containing membrane-associated guanylate kinase (MAGUK) family and was found to be a binding partner of BCL10 via CARD-CARD interaction (Bertin et al. 2001; Gaide et al. 2001), similar to CARD9 and the other member of CARD-MAGUKs, CARMA2 and CARMA3. Among the CARD-MAGUK families, only CARMA1 is highly and selectively expressed in lymphoid organs such as thymus, lymph node, and spleen. It is thought that CARMA1 binds to BCL10-  MALT1...
This is a preview of subscription content, log in to check access.


  1. Bertin J, Wang L, Guo Y, Jacobson MD, Poyet JL, Srinivasula SM, Merriam S, DiStefano PS, Alnemri ES. 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;276:11877–82.PubMedCrossRefGoogle Scholar
  2. Du MQ. MALT lymphoma: recent advances in aetiology and molecular genetics. J Clin Exp Hematop. 2007;47:31–42.PubMedCrossRefGoogle Scholar
  3. Gaide O, Martinon F, Micheau O, Bonnet D, Thome M, Tschopp J. Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation. FEBS Lett. 2001;496:121–7.PubMedCrossRefGoogle Scholar
  4. Gross O, Grupp C, Steinberg C, Zimmermann S, Strasser D, Hannesschlager N, Reindl W, Jonsson H, Huo H, Littman DR, et al. Multiple ITAM-coupled NK-cell receptors engage the Bcl10/Malt1 complex via CARMA1 for NF-kappaB and MAPK activation to selectively control cytokine production. Blood. 2008;112:2421–8.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Hara H, Saito T. CARD9 versus CARMA1 in innate and adaptive immunity. Trends Immunol. 2009;30:234–42.PubMedCrossRefGoogle Scholar
  6. Hara H, Wada T, Bakal C, Kozieradzki I, Suzuki S, Suzuki N, Nghiem M, Griffiths EK, Krawczyk C, Bauer B, et al. The MAGUK family protein CARD11 is essential for lymphocyte activation. Immunity. 2003;18:763–75.PubMedCrossRefGoogle Scholar
  7. Hara H, Ishihara C, Takeuchi A, Xue L, Morris SW, Penninger JM, Yoshida H, Saito T. Cell type-specific regulation of ITAM-mediated NF-kappaB activation by the adaptors, CARMA1 and CARD9. J Immunol. 2008;181:918–30.PubMedCrossRefGoogle Scholar
  8. Hara H, IIzasa E, Nakaya M, Yoshida H. L-CBM signaling in lymphocyte development and function. J Blood Med. 2010;1:93–104.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Kuo SH, Yeh PY, Chen LT, MS W, Lin CW, Yeh KH, Tzeng YS, Chen JY, Hsu PN, Lin JT, Cheng AL. Overexpression of B cell-activating factor of TNF family (BAFF) is associated with Helicobacter pylori-independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma. Blood. 2008;112:2927–34.PubMedCrossRefGoogle Scholar
  10. Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW, Dave SS, Zhao H, Xu W, Rosenwald A, et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science. 2008;319:1676–9.PubMedCrossRefGoogle Scholar
  11. Li Z, Wang H, Xue L, Shin DM, Roopenian D, Xu W, Qi CF, Sangster MY, Orihuela CJ, Tuomanen E, et al. Emu-BCL10 mice exhibit constitutive activation of both canonical and noncanonical NF-kappaB pathways generating marginal zone (MZ) B-cell expansion as a precursor to splenic MZ lymphoma. Blood. 2009;114:4158–68.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Long M, Park SG, Strickland I, Hayden MS, Ghosh S. Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor. Immunity. 2009;31:921–31.PubMedCrossRefGoogle Scholar
  13. Molinero LL, Yang J, Gajewski T, Abraham C, Farrar MA, Alegre ML. CARMA1 controls an early checkpoint in the thymic development of FoxP3+ regulatory T cells. J Immunol. 2009;182:6736–43.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Ngo VN, Davis RE, Lamy L, Yu X, Zhao H, Lenz G, Lam LT, Dave S, Yang L, Powell J, Staudt LM. A loss-of-function RNA interference screen for molecular targets in cancer. Nature. 2006;441:106–10.PubMedCrossRefGoogle Scholar
  15. Ruefli-Brasse AA, French DM, Dixit VM. Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase. Science. 2003;302:1581–4.PubMedCrossRefGoogle Scholar
  16. Ruland J, Duncan GS, Elia A, del Barco BI, Nguyen L, Plyte S, Millar DG, Bouchard D, Wakeham A, Ohashi PS, Mak TW. Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure. Cell. 2001;104:33–42.PubMedCrossRefGoogle Scholar
  17. Ruland J, Duncan GS, Wakeham A, Mak TW. Differential requirement for Malt1 in T and B cell antigen receptor signaling. Immunity. 2003;19:749–58.PubMedCrossRefGoogle Scholar
  18. Schmidt-Supprian M, Tian J, Grant EP, Pasparakis M, Maehr R, Ovaa H, Ploegh HL, Coyle AJ, Rajewsky K. Differential dependence of CD4 + CD25+ regulatory and natural killer-like T cells on signals leading to NF-kappaB activation. Proc Natl Acad Sci U S A. 2004;101:4566–71.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Tusche MW, Ward LA, Vu F, McCarthy D, Quintela-Fandino M, Ruland J, Gommerman JL, Mak TW. Differential requirement of MALT1 for BAFF-induced outcomes in B cell subsets. J Exp Med. 2009;206:2671–83.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Xue L, Morris SW, Orihuela C, Tuomanen E, Cui X, Wen R, Wang D. Defective development and function of Bcl10-deficient follicular, marginal zone and B1 B cells. Nat Immunol. 2003;4:857–65.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Division of Molecular and Cellular Immunoscience, Department of Biomolecular SciencesSaga UniversitySagaJapan