Home LiteratureArticle Details
PMID: 8306975 Published · ppublish English Journal Article

Dual role of the tyrosine activation motif of the Ig-alpha protein during signal transduction via the B cell antigen receptor.

The EMBO journal ·Vol. 13 ·No. 1 ·1994-01-01 ·Pages 83-9

Flaswinkel H, Reth M

Abstract

The B cell antigen receptor (BCR) is a multimeric protein complex consisting of the ligand binding immunoglobulin molecule and the Ig-alpha/beta heterodimer that mediates intracellular signalling by coupling the receptor to protein tyrosine kinases (PTKs). Transfection of the Ig-alpha deficient myeloma cell line J558L microns with expression vectors coding for mutated Ig-alpha allowed us to test the function of the tyrosines in the cytoplasmic region of Ig-alpha in the context of the BCR. Furthermore we expressed Ig-alpha mutations as chimeric CD8-Ig-alpha molecules on K46 B lymphoma cells and tested their signalling capacity in terms of PTK activation and release of calcium. We show here that the conserved tyrosine residues in the cytoplasmic portion of Ig-alpha have a dual role. First, they are required for efficient activation of PTKs during signal induction and second, one of them is subject to phosphorylation by activated src-related PTKs. Phosphorylation on tyrosine in the cytoplasmic portion of Ig-alpha is discussed as a possible mechanism to couple the BCR to SH2 domain-carrying molecules.

MeSH Terms
Amino Acid Sequence Animals Antigens, CD/chemistry,metabolism Base Sequence CD79 Antigens Cell Line DNA Mice Molecular Sequence Data Mutagenesis, Site-Directed Phosphorylation Protein-Tyrosine Kinases/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-fyn Receptors, Antigen, B-Cell/chemistry,metabolism Sequence Homology, Amino Acid Signal Transduction Transfection Tyrosine/metabolism
Chemicals
Antigens, CD CD79 Antigens Cd79a protein, mouse Proto-Oncogene Proteins Receptors, Antigen, B-Cell Tyrosine DNA Protein-Tyrosine Kinases Fyn protein, mouse Proto-Oncogene Proteins c-fyn
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Flaswinkel H
Max-Planck-Institut für Immunobiologie, Freiburg, Germany.
Reth M
References (58)
58 references, click to expand
  1. Human mb-1 gene: complete cDNA sequence and its expression in B cells bearing membrane Ig of various isotypes.
    J Immunol. 1992 Jan 15;148(2):633-7 PMID: 1729378
  2. Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-tyrosine kinase showing high susceptibility to proteolysis.
    J Biol Chem. 1991 Aug 25;266(24):15790-6 PMID: 1874735
  3. Protein tyrosine phosphorylation is induced in murine B lymphocytes in response to stimulation with anti-immunoglobulin.
    EMBO J. 1990 Jul;9(7):2125-31 PMID: 2357961
  4. Activation of T cells by a tyrosine kinase activation domain in the cytoplasmic tail of CD3 epsilon.
    Science. 1992 Jan 3;255(5040):79-82 PMID: 1532456
  5. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161-5 PMID: 6438633
  6. Sequence requirements for induction of cytolysis by the T cell antigen/Fc receptor zeta chain.
    Cell. 1992 Mar 6;68(5):889-97 PMID: 1547489
  7. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways.
    Cell. 1991 Mar 8;64(5):891-901 PMID: 1705867
  8. Raf-1 kinase is essential for early Xenopus development and mediates the induction of mesoderm by FGF.
    Cell. 1993 May 7;73(3):571-83 PMID: 7683975
  9. Quantitation of lymphocyte intracellular free calcium signals using indo-1.
    Cell Calcium. 1988 Jun;9(3):141-7 PMID: 3416353
  10. Signal transduction by immunoglobulin is mediated through Ig alpha and Ig beta.
    J Exp Med. 1993 Sep 1;178(3):1049-55 PMID: 7688784
  11. Regulation of B cell antigen receptor signal transduction and phosphorylation by CD45.
    Science. 1991 Jun 28;252(5014):1839-42 PMID: 1648262
  12. Molecular components of the B-cell antigen receptor complex of the IgM class.
    Nature. 1990 Feb 22;343(6260):760-2 PMID: 2304550
  13. The human Ig-beta cDNA sequence, a homologue of murine B29, is identical in B cell and plasma cell lines producing all the human Ig isotypes.
    J Immunol. 1993 Jan 15;150(2):491-8 PMID: 8419481
  14. 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
  15. Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor.
    Cell. 1993 May 7;73(3):611-20 PMID: 8490966
  16. Identification of tyrosine 67 in bovine brain myelin basic protein as a specific phosphorylation site for thymus p56lck.
    Biochem Biophys Res Commun. 1991 Aug 15;178(3):1393-9 PMID: 1714722
  17. Association of the 72-kDa protein-tyrosine kinase PTK72 with the B cell antigen receptor.
    J Biol Chem. 1992 Apr 25;267(12):8613-9 PMID: 1569106
  18. The zeta chain is associated with a tyrosine kinase and upon T-cell antigen receptor stimulation associates with ZAP-70, a 70-kDa tyrosine phosphoprotein.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9166-70 PMID: 1717999
  19. Signalling function of the B-cell antigen receptors.
    Immunol Rev. 1993 Apr;132:125-46 PMID: 8394280
  20. 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
  21. Differences in glycoprotein complexes associated with IgM and IgD on normal murine B cells potentially enable transduction of different signals.
    EMBO J. 1990 Jul;9(7):2117-24 PMID: 2357960
  22. The gamma subunit of the B cell antigen-receptor complex is a C-terminally truncated product of the B29 gene.
    J Immunol. 1993 Apr 1;150(7):2814-22 PMID: 8454858
  23. Transfected plasmacytoma cells do not transport the membrane form of IgM to the cell surface.
    J Exp Med. 1988 Feb 1;167(2):652-7 PMID: 3258011
  24. Identification of the genes encoding the IgM-alpha and Ig-beta components of the IgM antigen receptor complex by amino-terminal sequencing.
    Eur J Immunol. 1990 Dec;20(12):2795-9 PMID: 2269334
  25. T cell antigen receptor signal transduction: a tale of tails and cytoplasmic protein-tyrosine kinases.
    Cell. 1993 Apr 23;73(2):209-12 PMID: 8477442
  26. Deletion of the cytoplasmic region of the CD3 epsilon subunit does not prevent assembly of a functional T-cell receptor.
    Proc Natl Acad Sci U S A. 1989 Sep;86(18):7108-12 PMID: 2528731
  27. Molecular cloning of the Ig-alpha subunit of the human B-cell antigen receptor complex.
    Immunogenetics. 1992;36(4):266-9 PMID: 1639443
  28. A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos.
    Cell. 1993 Apr 9;73(1):179-91 PMID: 8462098
  29. SH2 domains recognize specific phosphopeptide sequences.
    Cell. 1993 Mar 12;72(5):767-78 PMID: 7680959
  30. Cloning and sequencing of the cDNA encoding the human homologue of the murine immunoglobulin-associated protein B29.
    Eur J Immunol. 1992 Jun;22(6):1621-5 PMID: 1534761
  31. B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties.
    EMBO J. 1988 Nov;7(11):3457-64 PMID: 2463161
  32. Membrane IgM and IgD molecules fail to transduce Ca2+ mobilizing signals when expressed on differentiated B lineage cells.
    J Immunol. 1990 May 1;144(9):3272-80 PMID: 2109774
  33. Molecular mimicry of the antigen receptor signalling motif by transmembrane proteins of the Epstein-Barr virus and the bovine leukaemia virus.
    Curr Biol. 1993 Jun 1;3(6):333-9 PMID: 15335726
  34. Molecular cloning and expression pattern of a human gene homologous to the murine mb-1 gene.
    J Immunol. 1992 Mar 1;148(5):1526-31 PMID: 1538135
  35. Tyrosine phosphorylation of band 3 inhibits peripheral protein binding.
    J Biol Chem. 1987 Apr 5;262(10):4592-6 PMID: 3558357
  36. B29: a member of the immunoglobulin gene superfamily exclusively expressed on beta-lineage cells.
    Proc Natl Acad Sci U S A. 1988 Sep;85(18):6890-4 PMID: 3137575
  37. 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
  38. Activation of V kappa gene rearrangement in pre-B cells follows the expression of membrane-bound immunoglobulin heavy chains.
    EMBO J. 1987 Nov;6(11):3299-305 PMID: 3123216
  39. 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
  40. Antigen receptor tail clue.
    Nature. 1989 Mar 30;338(6214):383-4 PMID: 2927501
  41. The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules.
    Cell. 1992 Jan 10;68(1):83-95 PMID: 1531041
  42. B lymphocyte antigen receptors (mIg) are non-covalently associated with a disulfide linked, inducibly phosphorylated glycoprotein complex.
    EMBO J. 1990 Feb;9(2):441-8 PMID: 2154371
  43. Differential signaling through the Ig-alpha and Ig-beta components of the B cell antigen receptor.
    Eur J Immunol. 1993 Apr;23(4):911-6 PMID: 7681402
  44. Tandem SH2 domains of ZAP-70 bind to T cell antigen receptor zeta and CD3 epsilon from activated Jurkat T cells.
    J Biol Chem. 1993 Sep 15;268(26):19797-801 PMID: 8366117
  45. p59fyn tyrosine kinase associates with multiple T-cell receptor subunits through its unique amino-terminal domain.
    Mol Cell Biol. 1992 Dec;12(12):5438-46 PMID: 1448076
  46. The B-cell antigen receptor of the five immunoglobulin classes.
    Nature. 1991 Aug 29;352(6338):777-81 PMID: 1881434
  47. A PCR method for introducing mutations into cloned DNA by joining an internal primer to a tagged flanking primer.
    Nucleic Acids Res. 1992 Feb 11;20(3):624 PMID: 1311079
  48. Identification of two distinct phosphoproteins as components of the human B cell antigen receptor complex.
    Eur J Immunol. 1990 Dec;20(12):2789-93 PMID: 2269333
  49. An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro.
    Cell. 1993 Apr 9;73(1):169-77 PMID: 8462097
  50. Association of B cell antigen receptor with protein tyrosine kinase Lyn.
    Science. 1991 Jan 11;251(4990):192-4 PMID: 1702903
  51. The CD3 zeta cytoplasmic domain mediates CD2-induced T cell activation.
    J Exp Med. 1992 Jul 1;176(1):139-45 PMID: 1351920
  52. T-cell and basophil activation through the cytoplasmic tail of T-cell-receptor zeta family proteins.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8905-9 PMID: 1833767
  53. Antigen receptors on B lymphocytes.
    Annu Rev Immunol. 1992;10:97-121 PMID: 1591006
  54. Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain.
    J Exp Med. 1993 Apr 1;177(4):1093-103 PMID: 8459204
  55. Tyrosine phosphorylation of components of the B-cell antigen receptors following receptor crosslinking.
    Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3436-40 PMID: 1707541
  56. Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides.
    Cell. 1991 Mar 8;64(5):1037-46 PMID: 1900456
  57. IgM antigen receptor complex contains phosphoprotein products of B29 and mb-1 genes.
    Proc Natl Acad Sci U S A. 1991 May 1;88(9):3982-6 PMID: 2023945
  58. Tyrosine kinases and tyrosine-based activation motifs. Current research on activation via the T cell antigen receptor.
    J Biol Chem. 1992 Dec 15;267(35):24913-6 PMID: 1459994
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-01-01
Pages
83-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC394781
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2