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PMID: 8755568 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Evidence for a preformed transducer complex organized by the B cell antigen receptor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 15 ·1996-07-23 ·Pages 7865-70

Wienands J, Larbolette O, Reth M

Abstract

The B cell antigen receptor (BCR) consists of the membrane-bound immunoglobulin (mIg) molecule and the Ig-alpha/Ig-beta heterodimer, which functions as signaling subunit of the receptor. Stimulation of the BCR activates protein tyrosine kinases (PTKs) that phosphorylate a number of substrate proteins, including the Ig-alpha/Ig-beta heterodimer of the BCR itself. How the PTKs become activated after BCR engagement is not known at present. Here, we show that BCR-negative J558L cells treated with the protein tyrosine phosphatase inhibitor pervanadate/H2O2 display only a weak substrate phosphorylation. However, in BCR-positive transfectants of J558L, treatment with pervanadate/H2O2 induces a strong phosphorylation of several substrate proteins. Treatment with pervanadate/H2O2 does not result in receptor crosslinking, yet the pattern of protein phosphorylation is similar to that observed after BCR stimulation by antigen. The response requires cellular integrity because tyrosine phosphorylation of most substrates is not visible in cell lysates. Cells that express a BCR containing an Ig-alpha subunit with a mutated immunoreceptor tyrosine-based activation motif display a delayed response. The data suggest that, once expressed on the surface, the BCR organizes protein tyrosine phosphatases, PTKs, and their substrates into a transducer complex that can be activated by pervanadate/H202 in the absence of BCR crosslinking. Assembly of this preformed complex seems to be a prerequisite for BCR-mediated signal transduction.

MeSH Terms
Animals Cell Line Enzyme Inhibitors/pharmacology Glycosylphosphatidylinositols Hydrogen Peroxide/pharmacology Immunoglobulin D/biosynthesis Immunoglobulin M/biosynthesis Kinetics Multiple Myeloma Phosphoproteins/isolation & purification,metabolism Phosphorylation Point Mutation Protein Tyrosine Phosphatases/antagonists & inhibitors Protein-Tyrosine Kinases/metabolism Receptors, Antigen, B-Cell/biosynthesis,immunology,physiology Recombinant Proteins/biosynthesis,immunology Signal Transduction Vanadates/pharmacology
Chemicals
Enzyme Inhibitors Glycosylphosphatidylinositols Immunoglobulin D Immunoglobulin M Phosphoproteins Receptors, Antigen, B-Cell Recombinant Proteins pervanadate Vanadates Hydrogen Peroxide Protein-Tyrosine Kinases Protein Tyrosine Phosphatases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wienands J
Max-Planck-Institüt fur Immunbiologie, Freiburg, Germany.
Larbolette O
Reth M
References (41)
41 references, click to expand
  1. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk.
    Nature. 1995 Nov 16;378(6554):298-302 PMID: 7477352
  2. Manipulation of B cell antigen receptor tyrosine phosphorylation using aluminum fluoride and sodium orthovanadate.
    Mol Immunol. 1995 Nov;32(16):1283-94 PMID: 8559152
  3. Molecular components of the B cell antigen receptor complex of class IgD differ partly from those of IgM.
    EMBO J. 1990 Feb;9(2):449-55 PMID: 2303036
  4. Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3631-5 PMID: 7682714
  5. A novel 34-kd protein co-isolated with the IgM molecule in surface IgM-expressing cells.
    EMBO J. 1988 Nov;7(11):3451-6 PMID: 3264786
  6. Activation of human peripheral blood T lymphocytes by pharmacological induction of protein-tyrosine phosphorylation.
    Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10306-10 PMID: 1279675
  7. In vitro characterization of major ligands for Src homology 2 domains derived from protein tyrosine kinases, from the adaptor protein SHC and from GTPase-activating protein in Ramos B cells.
    Eur J Immunol. 1994 Aug;24(8):1799-807 PMID: 7519995
  8. Syk tyrosine kinase required for mouse viability and B-cell development.
    Nature. 1995 Nov 16;378(6554):303-6 PMID: 7477353
  9. The internalization of the IgG2a antigen receptor does not require the association with Ig-alpha and Ig-beta but the activation of protein tyrosine kinases does.
    Eur J Immunol. 1994 Mar;24(3):665-71 PMID: 8125135
  10. Regulation of B cell antigen receptor signal transduction and phosphorylation by CD45.
    Science. 1991 Jun 28;252(5014):1839-42 PMID: 1648262
  11. Molecular components of the B-cell antigen receptor complex of the IgM class.
    Nature. 1990 Feb 22;343(6260):760-2 PMID: 2304550
  12. Association between B-lymphocyte membrane immunoglobulin and multiple members of the Src family of protein tyrosine kinases.
    Mol Cell Biol. 1992 May;12(5):2315-21 PMID: 1569953
  13. Tyrosine-phosphorylated forms of Ig beta, CD22, TCR zeta and HOSS are major ligands for tandem SH2 domains of Syk.
    Int Immunol. 1995 Nov;7(11):1701-8 PMID: 8580068
  14. CD38 signal transduction in human B cell precursors. Rapid induction of tyrosine phosphorylation, activation of syk tyrosine kinase, and phosphorylation of phospholipase C-gamma and phosphatidylinositol 3-kinase.
    J Immunol. 1996 Jan 1;156(1):100-7 PMID: 8598449
  15. B cell antigen receptor cross-linking induces tyrosine phosphorylation and membrane translocation of a multimeric Shc complex that is augmented by CD19 co-ligation.
    Eur J Immunol. 1994 Nov;24(11):2818-25 PMID: 7525306
  16. Recruitment and activation of PTP1C in negative regulation of antigen receptor signaling by Fc gamma RIIB1.
    Science. 1995 Apr 14;268(5208):293-7 PMID: 7716523
  17. Induction of tyrosine phosphorylation and T-cell activation by vanadate peroxide, an inhibitor of protein tyrosine phosphatases.
    Biochem J. 1994 Jan 1;297 ( Pt 1):163-73 PMID: 7506531
  18. Signalling function of the B-cell antigen receptors.
    Immunol Rev. 1993 Apr;132:125-46 PMID: 8394280
  19. Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases.
    Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7410-4 PMID: 1714601
  20. Stimulatory effects of the protein tyrosine phosphatase inhibitor, pervanadate, on T-cell activation events.
    J Biol Chem. 1993 Mar 15;268(8):5886-93 PMID: 8383678
  21. Selective inhibition of protein tyrosine phosphatase activities by H2O2 and vanadate in vitro.
    Biochem Biophys Res Commun. 1992 Oct 30;188(2):773-9 PMID: 1445322
  22. B-cell antigen receptor motifs have redundant signalling capabilities and bind the tyrosine kinases PTK72, Lyn and Fyn.
    Curr Biol. 1993 Oct 1;3(10):645-57 PMID: 15335855
  23. Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation.
    J Biol Chem. 1995 May 12;270(19):11590-4 PMID: 7538118
  24. Signal transduction by the B cell antigen receptor and its coreceptors.
    Annu Rev Immunol. 1994;12:457-86 PMID: 8011288
  25. Role of the Syk autophosphorylation site and SH2 domains in B cell antigen receptor signaling.
    J Exp Med. 1995 Dec 1;182(6):1815-23 PMID: 7500027
  26. Of ITAMs and ITIMs: turning on and off the B cell antigen receptor.
    J Exp Med. 1995 Jun 1;181(6):1953-6 PMID: 7539033
  27. Dual role of the tyrosine activation motif of the Ig-alpha protein during signal transduction via the B cell antigen receptor.
    EMBO J. 1994 Jan 1;13(1):83-9 PMID: 8306975
  28. Glycosyl-phosphatidylinositol linkage as a mechanism for cell-surface expression of immunoglobulin D.
    Nature. 1992 Mar 19;356(6366):246-8 PMID: 1313152
  29. Identification of the tyrosine phosphatase PTP1C as a B cell antigen receptor-associated protein involved in the regulation of B cell signaling.
    J Exp Med. 1995 Jun 1;181(6):2077-84 PMID: 7539038
  30. Genetic and mutational analysis of the T-cell antigen receptor.
    Annu Rev Immunol. 1990;8:139-67 PMID: 2188661
  31. The MB-1/B29 heterodimer couples the B cell antigen receptor to multiple src family protein tyrosine kinases.
    J Immunol. 1992 Sep 1;149(5):1548-55 PMID: 1506682
  32. The B cell antigen receptor complex: association of Ig-alpha and Ig-beta with distinct cytoplasmic effectors.
    Science. 1992 Oct 2;258(5079):123-6 PMID: 1439759
  33. The B cell antigen receptor of class IgD induces a stronger and more prolonged protein tyrosine phosphorylation than that of class IgM.
    J Exp Med. 1995 Mar 1;181(3):1005-14 PMID: 7869025
  34. Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease.
    Cell. 1995 Oct 20;83(2):301-11 PMID: 7585947
  35. Identification of components of the B cell antigen receptor complex.
    Adv Exp Med Biol. 1991;292:207-14 PMID: 1950772
  36. Antigen receptor tail clue.
    Nature. 1989 Mar 30;338(6214):383-4 PMID: 2927501
  37. The B-cell antigen receptor of the five immunoglobulin classes.
    Nature. 1991 Aug 29;352(6338):777-81 PMID: 1881434
  38. Association of B cell antigen receptor with protein tyrosine kinase Lyn.
    Science. 1991 Jan 11;251(4990):192-4 PMID: 1702903
  39. Antigen receptors on B lymphocytes.
    Annu Rev Immunol. 1992;10:97-121 PMID: 1591006
  40. Antigen-receptor induced clonal expansion and deletion of lymphocytes are impaired in mice lacking HS1 protein, a substrate of the antigen-receptor-coupled tyrosine kinases.
    EMBO J. 1995 Aug 1;14(15):3664-78 PMID: 7641686
  41. Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways.
    EMBO J. 1994 Mar 15;13(6):1341-9 PMID: 8137818
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.15.7865
Published
1996-07-23
Pages
7865-70
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38840
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.93.15.7865 PMC Full Text View journal details
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