본문 바로가기
KERD
논문KCI 등재

Heterogeneous Nuclear Ribonucleoprotein A2B1 Exerts a Regulatory Role in Lipopolysaccharide-stimulated 38B9 B Cell Activation

5

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

Major histocompatibility complex (MHC) class II molecules, which are recognized for their primary function of presenting an antigen to the T cell receptor, are involved in various signaling pathways in B cell activation. We identified heterogeneous nuclear ribonucleoprotein (hnRNP) A2B1 as an MHC class II molecule-associated protein involved in MHC class II-mediated signal transduction in lipopolysaccharide (LPS)-stimulated 38B9 B cells. Although the function of hnRNP A2B1 in the nucleus is primarily known, the level of hnRNP A2B1 in the cytoplasm was increased in LPS-stimulated 38B9 cells, while it was not detected in the cytoplasm of non-treated 38B9 cells. The silencing of hnRNP A2B1 expression using siRNA disturbed B cell maturation by regulation of mitogen-activated protein kinase signaling, NF-κB activation, and protein kinase B activation. These results suggest that hnRNP A2B1 is associated with MHC class II molecules and is involved in B cell activation signaling pathways in LPS-stimulated 38B9 cells.

Abstract

Major histocompatibility complex (MHC) class II molecules, which are recognized for their primary function of presenting an antigen to the T cell receptor, are involved in various signaling pathways in B cell activation. We identified heterogeneous nuclear ribonucleoprotein (hnRNP) A2B1 as an MHC class II molecule-associated protein involved in MHC class II-mediated signal transduction in lipopolysaccharide (LPS)-stimulated 38B9 B cells. Although the function of hnRNP A2B1 in the nucleus is primarily known, the level of hnRNP A2B1 in the cytoplasm was increased in LPS-stimulated 38B9 cells, while it was not detected in the cytoplasm of non-treated 38B9 cells. The silencing of hnRNP A2B1 expression using siRNA disturbed B cell maturation by regulation of mitogen-activated protein kinase signaling, NF-κB activation, and protein kinase B activation. These results suggest that hnRNP A2B1 is associated with MHC class II molecules and is involved in B cell activation signaling pathways in LPS-stimulated 38B9 cells.

참고문헌 (27)

  1. Zhang W, "MAPK signal pathways in the regulation of cell proliferation in mammalian cells", Cell Res, 12, pp.9~18 (2002)
  2. Huang G, "Regulation of JNK and p38 MAPK in the immune system: signal integration, propagation and termination", Cytokine, 48, pp.161~169 (2009)
  3. Khiem D, "A p38 MAPK-MEF2C pathway regulates B-cell proliferation", Proc Natl Acad Sci U S A, 105, pp.17067~17072 (2008)
  4. Limon JJ, "Akt and mTOR in B cell activation and differentiation", Front Immunol, 3, pp.228~ (2012)
  5. Huang H, "Dynamic FoxO transcription factors", J Cell Sci, 120, pp.2479~2487 (2007)
  6. Robinson JH, "Diversity in MHC class II antigen presentation", Immunology, 105, pp.252~262 (2002)
  7. Al-Daccak R, "MHC class II signaling in antigen-presenting cells", Curr Opin Immunol, 16, pp.108~113 (2004)
  8. Liu X, "Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk", Nat Immunol, 12, pp.416~424 (2011)
  9. Schneppenheim J, "The influence of MHC class II on B cell defects induced by invariant chain", CD74 N-terminal fragments, 2017, pp.199, 172~185
  10. Schneppenheim J, "Signal-peptide-peptidase-like 2a is required for CD74 intramembrane proteolysis in human B cells", Biochem Biophys Res Commun, 451, pp.48~53 (2014)
  11. Yang HY, "Rac", ROS-related protein kinase C and phosphatidylinositol-3-kinase signaling are involved in a negative regulating cascade in B cell activation by antibody-mediated cross-linking of MHC class II molecules, 2010, pp.47, 706~712
  12. Yang HY, "Pro-IL-16 is associated with MHC class II-mediated negative regulation of mouse resting B cell activation through MAP kinases, NF-κB and Skp2-dependent p27kip regulation", Scand J Immunol, 77, pp.177~186 (2013)
  13. Schlissel MS, "Activation of immunoglobulin kappa gene rearrangement correlates with induction of germline kappa gene transcription", Cell, 58, pp.1001~1007 (1989)
  14. Kim J, "Involvement of ERK, p38 MAP kinase, and PKC in MHC class II-mediated signal transduction in a resting B cell line", Biochem Biophys Res Commun, 291, pp.139~145 (2002)
  15. Choi HS, "Heterogeneous nuclear ribonucleoprotein A2", B1 regulates the self-renewal and pluripotency of human embryonic stem cells via the control of the G1, Stem Cells, pp.2013, 31[DOI]
  16. Gerondakis S, "Roles of the NF-κB pathway in lymphocyte development and function", Cold Spring Harb Perspect Biol, 2, pp.a000182~ (2010)
  17. Alt FW, "Ordered rearrangement of immunoglobulin heavy chain variable region segments", EMBO J, 3, pp.1209~1219 (1984)
  18. Krecic AM, "hnRNP complexes: composition, structure, and function", Curr Opin Cell Biol, 11, pp.363~371 (1999)
  19. Piñol-Roma S, "hnRNP proteins: localization and transport between the nucleus and the cytoplasm", Trends Cell Biol, 3, pp.151~155 (1993)
  20. Hernández-Díaz I, "Heterogeneous nuclear ribonucleoprotein A2", B1 is a tissue-specific aldosterone target gene with prominent induction in the rat distal colon, 2013, pp.304, G122~G131
  21. Hayashi EA, "Role of TLR in B cell development: signaling through TLR4 promotes B cell maturation and is inhibited by TLR2", J Immunol, 174, pp.6639~6647 (2005)
  22. Feng B, "NF-κB inhibitor blocks B cell development at two checkpoints", Med Immunol, 3, pp.1~ (2004)
  23. Faes S, "PI3K and AKT: unfaithful partners in cancer", Int J Mol Sci, 16, pp.21138~21152 (2015)
  24. Vikström IB, "MCL-1 is required throughout B-cell development and its loss sensitizes specific B-cell subsets to inhibition of BCL-2 or BCL-XL", Cell Death Dis, 7, pp.e2345~ (2016)
  25. Shilo A, "Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development", RNA, 20, pp.505~515 (2014)
  26. Kim HJ, "Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS", Nature, 495, pp.467~473 (2013)
  27. Lemieux B, "A function for the hnRNP A1", A2 proteins in transcription elongation, 2015, pp.10, e0126654~

관련 논문AI추천

이 간행물의 다른 논문 (8건)