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PMID: 1321296 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

An Epstein-Barr virus transformation-associated membrane protein interacts with src family tyrosine kinases.

Journal of virology ·Vol. 66 ·No. 8 ·1992-08-00 ·Pages 5161-7

Burkhardt AL, Bolen JB, Kieff E, Longnecker R

Abstract

In latently infected growth-transformed human lymphocytes, Epstein-Barr virus (EBV) encodes two integral plasma membrane proteins: LMP1, which constitutively induces B-lymphocyte activation and intercellular adhesion, and LMP2A, which associates with LMP1 and is a tyrosine kinase substrate. We now demonstrate that LMP2A associates with src family protein tyrosine kinases, particularly lyn kinase, in nonionic detergent extracts of transfected B lymphoma cells or in extracts of EBV-transformed B lymphocytes. The LMP2A and tyrosine kinase association is stable in nonionic detergents and includes a 70-kDa cell protein which is also an in vitro or in vivo kinase substrate. This LMP2A association with B-lymphocyte src family tyrosine kinases is likely to be an important pathway in EBV's effects on cell growth.

Related Genes
src
MeSH Terms
Animals Antigens, Viral/genetics,isolation & purification,metabolism B-Lymphocytes Cell Line Cell Transformation, Viral Genes, src Herpesvirus 4, Human/metabolism Lymphoma, B-Cell Membrane Proteins/genetics,isolation & purification,metabolism Oncogene Protein pp60(v-src)/isolation & purification,metabolism Protein Binding Protein-Tyrosine Kinases/isolation & purification,metabolism Transfection Viral Matrix Proteins Viral Proteins/genetics,isolation & purification,metabolism
Chemicals
Antigens, Viral EBV-associated membrane antigen, Epstein-Barr virus Membrane Proteins Viral Matrix Proteins Viral Proteins Protein-Tyrosine Kinases Oncogene Protein pp60(v-src)
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Burkhardt A L
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
Bolen J B
Kieff E
Longnecker R
References (70)
70 references, click to expand
  1. Cellular proteins that associate with the middle and small T antigens of polyomavirus.
    J Virol. 1988 Nov;62(11):3934-40 PMID: 2845116
  2. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation.
    Nature. 1985 May 16-22;315(6016):239-42 PMID: 2987699
  3. Association of the polyomavirus middle-T antigen with c-yes protein.
    Nature. 1987 Jan 8-14;325(7000):171-3 PMID: 3027584
  4. Identification and characterization of p59fyn (a src-like protein tyrosine kinase) in normal and polyoma virus transformed cells.
    EMBO J. 1988 Dec 1;7(12):3837-44 PMID: 3061807
  5. Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain.
    Cell. 1987 Apr 10;49(1):83-91 PMID: 3103927
  6. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck.
    Cell. 1988 Oct 21;55(2):301-8 PMID: 3262426
  7. Nucleotide sequence of an mRNA transcribed in latent growth-transforming virus infection indicates that it may encode a membrane protein.
    J Virol. 1984 Aug;51(2):411-9 PMID: 6086953
  8. Transformation of rat cells by an altered polyoma virus genome expressing only the middle-T protein.
    Nature. 1981 Aug 13;292(5824):595-600 PMID: 6265803
  9. The complex of polyoma virus middle-T antigen and pp60c-src.
    EMBO J. 1984 Mar;3(3):585-91 PMID: 6325177
  10. Stimulation of protein tyrosine phosphorylation by the B-lymphocyte antigen receptor.
    Nature. 1990 Jun 28;345(6278):810-3 PMID: 1694265
  11. Association between the PDGF receptor and members of the src family of tyrosine kinases.
    Cell. 1990 Aug 10;62(3):481-92 PMID: 1696179
  12. 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
  13. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins.
    Science. 1991 May 3;252(5006):668-74 PMID: 1708916
  14. 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
  15. Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma.
    Lancet. 1990 Jan 20;335(8682):128-30 PMID: 1967431
  16. 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
  17. 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
  18. Binding of GAP to activated PDGF receptors.
    Science. 1990 Mar 30;247(4950):1578-81 PMID: 2157284
  19. A second Epstein-Barr virus membrane protein (LMP2) is expressed in latent infection and colocalizes with LMP1.
    J Virol. 1990 May;64(5):2319-26 PMID: 2157888
  20. Identification of Epstein-Barr virus terminal protein 1 (TP1) in extracts of four lymphoid cell lines, expression in insect cells, and detection of antibodies in human sera.
    J Virol. 1990 Jun;64(6):2759-67 PMID: 2159542
  21. Phosphorylation of the PDGF receptor beta subunit creates a tight binding site for phosphatidylinositol 3 kinase.
    EMBO J. 1990 Oct;9(10):3279-86 PMID: 2170111
  22. Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors.
    Science. 1990 Nov 16;250(4983):979-82 PMID: 2173144
  23. 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
  24. 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
  25. Altered sites of tyrosine phosphorylation in pp60c-src associated with polyomavirus middle tumor antigen.
    Mol Cell Biol. 1986 May;6(5):1562-70 PMID: 2431281
  26. An 81 kd protein complexed with middle T antigen and pp60c-src: a possible phosphatidylinositol kinase.
    Cell. 1987 Sep 25;50(7):1031-7 PMID: 2441879
  27. Potential positive and negative autoregulation of p60c-src by intermolecular autophosphorylation.
    Proc Natl Acad Sci U S A. 1988 Jun;85(12):4232-6 PMID: 2454466
  28. Role of phosphatidylinositol kinase in PDGF receptor signal transduction.
    Science. 1989 Mar 3;243(4895):1191-4 PMID: 2466336
  29. Direct activation of the serine/threonine kinase activity of Raf-1 through tyrosine phosphorylation by the PDGF beta-receptor.
    Cell. 1989 Aug 25;58(4):649-57 PMID: 2475255
  30. A survey of Epstein-Barr virus DNA in lymphoid tissue. Frequent detection in Hodgkin's disease.
    Am J Clin Pathol. 1989 Jan;91(1):1-5 PMID: 2535912
  31. Association of p60fyn with middle tumor antigen in murine polyomavirus-transformed rat cells.
    J Virol. 1989 May;63(5):2343-7 PMID: 2539523
  32. Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization.
    Blood. 1989 Aug 1;74(2):810-6 PMID: 2546633
  33. Characterization of the BNLF-1 oncogene of Epstein-Barr virus.
    Curr Top Microbiol Immunol. 1989;144:233-9 PMID: 2551585
  34. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease.
    N Engl J Med. 1989 Oct 19;321(16):1080-5 PMID: 2552313
  35. Molecular genetic analysis of lymphoid tumors arising after organ transplantation.
    Am J Pathol. 1989 Dec;135(6):977-87 PMID: 2556930
  36. Epstein-Barr virus latent membrane protein: induction of B-cell activation antigens and membrane patch formation does not require vimentin.
    J Virol. 1989 Sep;63(9):4051-4 PMID: 2668563
  37. Evidence for two distinct phosphatidylinositol kinases in fibroblasts. Implications for cellular regulation.
    Biochem J. 1987 Oct 1;247(1):165-74 PMID: 2825654
  38. A spliced Epstein-Barr virus gene expressed in immortalized lymphocytes is created by circularization of the linear viral genome.
    EMBO J. 1988 Mar;7(3):769-74 PMID: 2840285
  39. Epstein-Barr virus latent infection membrane protein alters the human B-lymphocyte phenotype: deletion of the amino terminus abolishes activity.
    J Virol. 1988 Nov;62(11):4173-84 PMID: 2845129
  40. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells.
    Cell. 1985 Dec;43(3 Pt 2):831-40 PMID: 3000618
  41. Mutations around the NG59 lesion indicate an active association of polyoma virus middle-T antigen with pp60c-src is required for cell transformation.
    EMBO J. 1986 Feb;5(2):325-34 PMID: 3011402
  42. Signal transduction from membrane to cytoplasm: growth factors and membrane-bound oncogene products increase Raf-1 phosphorylation and associated protein kinase activity.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):8855-9 PMID: 3057494
  43. Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation.
    Cell. 1987 Apr 10;49(1):65-73 PMID: 3103925
  44. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src.
    Cell. 1987 Apr 10;49(1):75-82 PMID: 3103926
  45. Analysis of the c-src gene product structure, abundance, and protein kinase activity in human neuroblastoma and glioblastoma cells.
    Oncogene Res. 1987;2(1):1-18 PMID: 3146045
  46. Malignant lymphoma in cottontop marmosets after inoculation with Epstein-Barr virus.
    Proc Natl Acad Sci U S A. 1973 Sep;70(9):2487-91 PMID: 4354852
  47. Enhancement of cellular src gene product associated tyrosyl kinase activity following polyoma virus infection and transformation.
    Cell. 1984 Oct;38(3):767-77 PMID: 6091900
  48. A membrane protein encoded by Epstein-Barr virus in latent growth-transforming infection.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):7207-11 PMID: 6095274
  49. Polyoma virus transforming protein associates with the product of the c-src cellular gene.
    Nature. 1983 Jun 2-8;303(5916):435-9 PMID: 6304524
  50. The nature of Hodgkin and Reed-Sternberg cells, their association with EBV, and their relationship to anaplastic large-cell lymphoma.
    Ann Oncol. 1991 Feb;2 Suppl 2:33-8 PMID: 1646624
  51. Tyrosine phosphorylation coupled to IgE receptor-mediated signal transduction and histamine release.
    Proc Natl Acad Sci U S A. 1990 Jul;87(14):5327-30 PMID: 1695377
  52. Association of B cell antigen receptor with protein tyrosine kinase Lyn.
    Science. 1991 Jan 11;251(4990):192-4 PMID: 1702903
  53. An Epstein-Barr virus protein associated with cell growth transformation interacts with a tyrosine kinase.
    J Virol. 1991 Jul;65(7):3681-92 PMID: 1710288
  54. The B-cell antigen receptor complex.
    Immunol Today. 1991 Jun;12(6):196-201 PMID: 1878135
  55. Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A.
    Cell. 1990 Jan 12;60(1):167-76 PMID: 2153055
  56. PDGF beta-receptor stimulates tyrosine phosphorylation of GAP and association of GAP with a signaling complex.
    Cell. 1990 Apr 6;61(1):125-33 PMID: 2156626
  57. Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23.
    J Virol. 1990 May;64(5):2309-18 PMID: 2157887
  58. Identification of the Epstein-Barr virus terminal protein gene products in latently infected lymphocytes.
    J Virol. 1990 Jun;64(6):2866-75 PMID: 2159547
  59. Detection of EBV gene expression in Reed-Sternberg cells of Hodgkin's disease.
    Int J Cancer. 1990 Nov 15;46(5):801-4 PMID: 2172169
  60. Molecular components of the B-cell antigen receptor complex of the IgM class.
    Nature. 1990 Feb 22;343(6260):760-2 PMID: 2304550
  61. 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
  62. Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity.
    Cell. 1987 Sep 25;50(7):1021-9 PMID: 2441878
  63. Peptide antibodies to the human c-fyn gene product demonstrate pp59c-fyn is capable of complex formation with the middle-T antigen of polyomavirus.
    EMBO J. 1988 Dec 1;7(12):3845-55 PMID: 2463167
  64. EGF induces tyrosine phosphorylation of phospholipase C-II: a potential mechanism for EGF receptor signaling.
    Cell. 1989 Jun 30;57(7):1101-7 PMID: 2472218
  65. Two related Epstein-Barr virus membrane proteins are encoded by separate genes.
    J Virol. 1989 Feb;63(2):933-7 PMID: 2536113
  66. CD3-negative lymphoproliferative disease of granular lymphocytes containing Epstein-Barr viral DNA.
    J Clin Invest. 1989 Jul;84(1):51-5 PMID: 2544630
  67. Plasma cell malignancy in the acquired immune deficiency syndrome. Association with Epstein-Barr virus.
    Am J Clin Pathol. 1989 Aug;92(2):222-8 PMID: 2547309
  68. Human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) antigens and genome in lymph nodes of HIV-positive patients affected by persistent generalized lymphadenopathy (PGL).
    Am J Clin Pathol. 1989 Dec;92(6):729-35 PMID: 2556016
  69. High frequency of Epstein-Barr virus genome in HIV-positive patients with Hodgkin's disease.
    Lancet. 1989 Jun 24;1(8652):1458 PMID: 2567472
  70. Transformation of Balb 3T3 cells by the BNLF-1 gene of Epstein-Barr virus.
    Oncogene. 1988 May;2(5):461-7 PMID: 2836780
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1992-08-00
Pages
5161-7
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC241398
Subset
IM
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