Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Feb 1;89(3):1118–1122. doi: 10.1073/pnas.89.3.1118

Activation of Src-like protein-tyrosine kinase Lyn and its association with phosphatidylinositol 3-kinase upon B-cell antigen receptor-mediated signaling.

Y Yamanashi 1, Y Fukui 1, B Wongsasant 1, Y Kinoshita 1, Y Ichimori 1, K Toyoshima 1, T Yamamoto 1
PMCID: PMC48397  PMID: 1371009

Abstract

Crosslinking of membrane-bound immunoglobulins, which are B-cell antigen receptors, causes proliferation and differentiation of B cells or the inhibition of their growth. The receptor-mediated signaling involves tyrosine phosphorylation of cellular proteins. The Src-like protein-tyrosine kinase Lyn is expressed preferentially in B cells and is an intracytoplasmic constituent of the B-cell antigen receptor complex. Crosslinking of membrane-bound immunoglobulin M with antibody induced rapid increases in the kinase activities of Lyn and Lyn-associated phosphatidylinositol 3-kinase. Crosslinking of B-cell antigen receptor also induced association of Lyn with an 85-kDa noncatalytic subunit of phosphatidylinositol 3-kinase. Thus, Lyn is functionally associated with membrane-bound immunoglobulin M and seems likely to participate in B-cell antigen receptor-mediated signaling.

Full text

PDF
1118

Images in this article

1120Image
on p.1120
1120Image
on p.1120
1120Image
on p.1120
1120Image
on p.1120
1120Image
on p.1120
1120Image
on p.1120
1120Image
on p.1120
1121Image
on p.1121
1121Image
on p.1121
1121Image
on p.1121
1121Image
on p.1121

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abraham N., Miceli M. C., Parnes J. R., Veillette A. Enhancement of T-cell responsiveness by the lymphocyte-specific tyrosine protein kinase p56lck. Nature. 1991 Mar 7;350(6313):62–66. doi: 10.1038/350062a0. [DOI] [PubMed] [Google Scholar]
  2. Arasi V. E., Lieberman R., Sandlund J., Kiwanuka J., Novikovs L., Kirsch I., Hollis G., Magrath I. T. Antiimmunoglobulin inhibition of Burkitt's lymphoma cell proliferation and concurrent reduction of c-myc and mu heavy chain gene expression. Cancer Res. 1989 Jun 15;49(12):3235–3241. [PubMed] [Google Scholar]
  3. Barber E. K., Dasgupta J. D., Schlossman S. F., Trevillyan J. M., Rudd C. E. The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. Proc Natl Acad Sci U S A. 1989 May;86(9):3277–3281. doi: 10.1073/pnas.86.9.3277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bijsterbosch M. K., Meade C. J., Turner G. A., Klaus G. G. B lymphocyte receptors and polyphosphoinositide degradation. Cell. 1985 Jul;41(3):999–1006. doi: 10.1016/s0092-8674(85)80080-5. [DOI] [PubMed] [Google Scholar]
  5. Boyd A. W., Schrader J. W. The regulation of growth and differentiation of a murine B cell lymphoma. II. The inhibition of WEHI 231 by anti-immunoglobulin antibodies. J Immunol. 1981 Jun;126(6):2466–2469. [PubMed] [Google Scholar]
  6. Burkhardt A. L., Brunswick M., Bolen J. B., Mond J. J. Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7410–7414. doi: 10.1073/pnas.88.16.7410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cambier J. C., Morrison D. C., Chien M. M., Lehmann K. R. Modeling of T cell contact-dependent B cell activation. IL-4 and antigen receptor ligation primes quiescent B cells to mobilize calcium in response to Ia cross-linking. J Immunol. 1991 Apr 1;146(7):2075–2082. [PubMed] [Google Scholar]
  8. Campbell K. S., Cambier J. C. B lymphocyte antigen receptors (mIg) are non-covalently associated with a disulfide linked, inducibly phosphorylated glycoprotein complex. EMBO J. 1990 Feb;9(2):441–448. doi: 10.1002/j.1460-2075.1990.tb08129.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Campbell K. S., Hager E. J., Friedrich R. J., Cambier J. C. 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):3982–3986. doi: 10.1073/pnas.88.9.3982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Campbell M. A., Sefton B. M. Protein tyrosine phosphorylation is induced in murine B lymphocytes in response to stimulation with anti-immunoglobulin. EMBO J. 1990 Jul;9(7):2125–2131. doi: 10.1002/j.1460-2075.1990.tb07381.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cantley L. C., Auger K. R., Carpenter C., Duckworth B., Graziani A., Kapeller R., Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281–302. doi: 10.1016/0092-8674(91)90639-g. [DOI] [PubMed] [Google Scholar]
  12. Carter R. H., Park D. J., Rhee S. G., Fearon D. T. Tyrosine phosphorylation of phospholipase C induced by membrane immunoglobulin in B lymphocytes. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2745–2749. doi: 10.1073/pnas.88.7.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cheng H. L., Blattner F. R., Fitzmaurice L., Mushinski J. F., Tucker P. W. Structure of genes for membrane and secreted murine IgD heavy chains. Nature. 1982 Apr 1;296(5856):410–415. doi: 10.1038/296410a0. [DOI] [PubMed] [Google Scholar]
  14. Cooke M. P., Abraham K. M., Forbush K. A., Perlmutter R. M. Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn). Cell. 1991 Apr 19;65(2):281–291. doi: 10.1016/0092-8674(91)90162-r. [DOI] [PubMed] [Google Scholar]
  15. Defranco A. L., Raveche E. S., Asofsky R., Paul W. E. Frequency of B lymphocytes responsive to anti-immunoglobulin. J Exp Med. 1982 May 1;155(5):1523–1536. doi: 10.1084/jem.155.5.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Escobedo J. A., Navankasattusas S., Kavanaugh W. M., Milfay D., Fried V. A., Williams L. T. cDNA cloning of a novel 85 kd protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF beta-receptor. Cell. 1991 Apr 5;65(1):75–82. doi: 10.1016/0092-8674(91)90409-r. [DOI] [PubMed] [Google Scholar]
  17. Fukui Y., Hanafusa H. Requirement of phosphatidylinositol-3 kinase modification for its association with p60src. Mol Cell Biol. 1991 Apr;11(4):1972–1979. doi: 10.1128/mcb.11.4.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fukui Y., Kornbluth S., Jong S. M., Wang L. H., Hanafusa H. Phosphatidylinositol kinase type I activity associates with various oncogene products. Oncogene Res. 1989;4(4):283–292. [PubMed] [Google Scholar]
  19. Gold M. R., Jakway J. P., DeFranco A. L. Involvement of a guanine-nucleotide-binding component in membrane IgM-stimulated phosphoinositide breakdown. J Immunol. 1987 Dec 1;139(11):3604–3613. [PubMed] [Google Scholar]
  20. Gold M. R., Law D. A., DeFranco A. L. Stimulation of protein tyrosine phosphorylation by the B-lymphocyte antigen receptor. Nature. 1990 Jun 28;345(6278):810–813. doi: 10.1038/345810a0. [DOI] [PubMed] [Google Scholar]
  21. Gold M. R., Matsuuchi L., Kelly R. B., DeFranco A. L. 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):3436–3440. doi: 10.1073/pnas.88.8.3436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Graziadei L., Riabowol K., Bar-Sagi D. Co-capping of ras proteins with surface immunoglobulins in B lymphocytes. Nature. 1990 Sep 27;347(6291):396–400. doi: 10.1038/347396a0. [DOI] [PubMed] [Google Scholar]
  23. Grupp S. A., Harmony J. A. Increased phosphatidylinositol metabolism is an important but not an obligatory early event in B lymphocyte activation. J Immunol. 1985 Jun;134(6):4087–4094. [PubMed] [Google Scholar]
  24. Harnett M. M., Klaus G. G. G protein coupling of antigen receptor-stimulated polyphosphoinositide hydrolysis in B cells. J Immunol. 1988 May 1;140(9):3135–3139. [PubMed] [Google Scholar]
  25. Hatakeyama M., Kono T., Kobayashi N., Kawahara A., Levin S. D., Perlmutter R. M., Taniguchi T. Interaction of the IL-2 receptor with the src-family kinase p56lck: identification of novel intermolecular association. Science. 1991 Jun 14;252(5012):1523–1528. doi: 10.1126/science.2047859. [DOI] [PubMed] [Google Scholar]
  26. Hombach J., Tsubata T., Leclercq L., Stappert H., Reth M. Molecular components of the B-cell antigen receptor complex of the IgM class. Nature. 1990 Feb 22;343(6260):760–762. doi: 10.1038/343760a0. [DOI] [PubMed] [Google Scholar]
  27. Hunter T., Cooper J. A. Protein-tyrosine kinases. Annu Rev Biochem. 1985;54:897–930. doi: 10.1146/annurev.bi.54.070185.004341. [DOI] [PubMed] [Google Scholar]
  28. Justement L. B., Campbell K. S., Chien N. C., Cambier J. C. Regulation of B cell antigen receptor signal transduction and phosphorylation by CD45. Science. 1991 Jun 28;252(5014):1839–1842. doi: 10.1126/science.1648262. [DOI] [PubMed] [Google Scholar]
  29. Kakiuchi T., Mizuguchi J., Nariuchi H. Molecular analysis of the dissociation between IL-2 production and proliferation in a response of a T cell clone to the antigen presented by B cells. J Immunol. 1988 Nov 15;141(10):3278–3284. [PubMed] [Google Scholar]
  30. Klaus G. G., Bijsterbosch M. K., O'Garra A., Harnett M. M., Rigley K. P. Receptor signalling and crosstalk in B lymphocytes. Immunol Rev. 1987 Oct;99:19–38. doi: 10.1111/j.1600-065x.1987.tb01170.x. [DOI] [PubMed] [Google Scholar]
  31. Matsuda M., Mayer B. J., Fukui Y., Hanafusa H. Binding of transforming protein, P47gag-crk, to a broad range of phosphotyrosine-containing proteins. Science. 1990 Jun 22;248(4962):1537–1539. doi: 10.1126/science.1694307. [DOI] [PubMed] [Google Scholar]
  32. Mizuguchi J., Tsang W., Morrison S. L., Beaven M. A., Paul W. E. Membrane IgM, IgD, and IgG act as signal transmission molecules in a series of B lymphomas. J Immunol. 1986 Oct 1;137(7):2162–2167. [PubMed] [Google Scholar]
  33. Monroe J. G., Haldar S. Involvement of a specific guanine nucleotide binding protein in receptor immunoglobulin stimulated inositol phospholipid hydrolysis. Biochim Biophys Acta. 1989 Oct 9;1013(3):273–278. doi: 10.1016/0167-4889(89)90146-8. [DOI] [PubMed] [Google Scholar]
  34. Otsu M., Hiles I., Gout I., Fry M. J., Ruiz-Larrea F., Panayotou G., Thompson A., Dhand R., Hsuan J., Totty N. Characterization of two 85 kd proteins that associate with receptor tyrosine kinases, middle-T/pp60c-src complexes, and PI3-kinase. Cell. 1991 Apr 5;65(1):91–104. doi: 10.1016/0092-8674(91)90411-q. [DOI] [PubMed] [Google Scholar]
  35. Rogers J., Early P., Carter C., Calame K., Bond M., Hood L., Wall R. Two mRNAs with different 3' ends encode membrane-bound and secreted forms of immunoglobulin mu chain. Cell. 1980 Jun;20(2):303–312. doi: 10.1016/0092-8674(80)90616-9. [DOI] [PubMed] [Google Scholar]
  36. Ruderman N. B., Kapeller R., White M. F., Cantley L. C. Activation of phosphatidylinositol 3-kinase by insulin. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1411–1415. doi: 10.1073/pnas.87.4.1411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Samelson L. E., Phillips A. F., Luong E. T., Klausner R. D. Association of the fyn protein-tyrosine kinase with the T-cell antigen receptor. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358–4362. doi: 10.1073/pnas.87.11.4358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shibasaki F., Homma Y., Takenawa T. Two types of phosphatidylinositol 3-kinase from bovine thymus. Monomer and heterodimer form. J Biol Chem. 1991 May 5;266(13):8108–8114. [PubMed] [Google Scholar]
  39. Skolnik E. Y., Margolis B., Mohammadi M., Lowenstein E., Fischer R., Drepps A., Ullrich A., Schlessinger J. Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases. Cell. 1991 Apr 5;65(1):83–90. doi: 10.1016/0092-8674(91)90410-z. [DOI] [PubMed] [Google Scholar]
  40. Stanley E., Ralph S., McEwen S., Boulet I., Holtzman D. A., Lock P., Dunn A. R. Alternatively spliced murine lyn mRNAs encode distinct proteins. Mol Cell Biol. 1991 Jul;11(7):3399–3406. doi: 10.1128/mcb.11.7.3399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tyler B. M., Cowman A. F., Gerondakis S. D., Adams J. M., Bernard O. mRNA for surface immunoglobulin gamma chains encodes a highly conserved transmembrane sequence and a 28-residue intracellular domain. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2008–2012. doi: 10.1073/pnas.79.6.2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Ullrich A., Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990 Apr 20;61(2):203–212. doi: 10.1016/0092-8674(90)90801-k. [DOI] [PubMed] [Google Scholar]
  43. Varticovski L., Druker B., Morrison D., Cantley L., Roberts T. The colony stimulating factor-1 receptor associates with and activates phosphatidylinositol-3 kinase. Nature. 1989 Dec 7;342(6250):699–702. doi: 10.1038/342699a0. [DOI] [PubMed] [Google Scholar]
  44. Veillette A., Bookman M. A., Horak E. M., Samelson L. E., Bolen J. B. Signal transduction through the CD4 receptor involves the activation of the internal membrane tyrosine-protein kinase p56lck. Nature. 1989 Mar 16;338(6212):257–259. doi: 10.1038/338257a0. [DOI] [PubMed] [Google Scholar]
  45. Wang J. Y. Isolation of antibodies for phosphotyrosine by immunization with a v-abl oncogene-encoded protein. Mol Cell Biol. 1985 Dec;5(12):3640–3643. doi: 10.1128/mcb.5.12.3640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wienands J., Hombach J., Radbruch A., Riesterer C., Reth M. Molecular components of the B cell antigen receptor complex of class IgD differ partly from those of IgM. EMBO J. 1990 Feb;9(2):449–455. doi: 10.1002/j.1460-2075.1990.tb08130.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Yamanashi Y., Fukushige S., Semba K., Sukegawa J., Miyajima N., Matsubara K., Yamamoto T., Toyoshima K. The yes-related cellular gene lyn encodes a possible tyrosine kinase similar to p56lck. Mol Cell Biol. 1987 Jan;7(1):237–243. doi: 10.1128/mcb.7.1.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Yamanashi Y., Kakiuchi T., Mizuguchi J., Yamamoto T., Toyoshima K. Association of B cell antigen receptor with protein tyrosine kinase Lyn. Science. 1991 Jan 11;251(4990):192–194. doi: 10.1126/science.1702903. [DOI] [PubMed] [Google Scholar]
  49. Yamanashi Y., Mori S., Yoshida M., Kishimoto T., Inoue K., Yamamoto T., Toyoshima K. Selective expression of a protein-tyrosine kinase, p56lyn, in hematopoietic cells and association with production of human T-cell lymphotropic virus type I. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6538–6542. doi: 10.1073/pnas.86.17.6538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Yamawaki-Kataoka Y., Nakai S., Miyata T., Honjo T. Nucleotide sequences of gene segments encoding membrane domains of immunoglobulin gamma chains. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2623–2627. doi: 10.1073/pnas.79.8.2623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Yi T. L., Bolen J. B., Ihle J. N. Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus. Mol Cell Biol. 1991 May;11(5):2391–2398. doi: 10.1128/mcb.11.5.2391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Zitron I. M., Clevinger B. L. Regulation of murine B cells through surface immunoglobulin. I. Monoclonal anti-delta antibody that induces allotype-specific proliferation. J Exp Med. 1980 Nov 1;152(5):1135–1146. doi: 10.1084/jem.152.5.1135. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES