Integral membrane protein 2 of Epstein-barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases

Cheryl L. Miller; Anne L. Burkhardt; Jennifer H. Lee; Becky Stealey; Richard Longnecker; Joseph B. Bolen; Elliott Kieff

doi:10.1016/S1074-7613(95)80040-9

Integral membrane protein 2 of Epstein-barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases

Cheryl L. Miller^*, Anne L. Burkhardt, Jennifer H. Lee, Becky Stealey, Richard Longnecker, Joseph B. Bolen, Elliott Kieff

^*Corresponding author for this work

Microbiology-Immunology

Research output: Contribution to journal › Article › peer-review

275 Scopus citations

Abstract

An Epstein-Barr virus-encoded protein, LMP2, blocks the effects of surface immunoglobulin (slg) cross-linking on calcium mobilization and on lytic reactivation of EBV in latently infected and growth-transformed primary human B lymphocytes. In wild-type EBV-transformed cells, LMP2 is constitutively tyrosine phosphorylated and is associated with Lyn and Syk protein-tyrosine kinases (PTKs). Baseline Lyn PTK activity is substantially reduced, and slg cross-linking fails to activate Lyn, Syk, P13-K, PLCγ2, Vav, Shc, and MAPK. Syk, P13-K, PLCγ2, and Vav are constitutively tyrosine phosphorylated, and their tyrosine phosphorylation does not change following sIg cross-linking. In contrast, cross-linking sIg on cells transformed by LMP2 null mutant EBV recombinants triggers the same protein tyrosine kinase cascade as in noninfected B lymphocytes. These data are consistent with a model in which LMP2 is a constitutive dominant negative modulator of slg receptor signaling through its effects on Lyn, Syk, or regulators of these kinases.

Original language	English (US)
Pages (from-to)	155-166
Number of pages	12
Journal	Immunity
Volume	2
Issue number	2
DOIs	https://doi.org/10.1016/S1074-7613(95)80040-9
State	Published - Feb 1995

Funding

This work was supported by grant 47006 from the National Cancer Institute. R. L, is a Special Fellow of the Leukemia Society of America, and iS supported by the Leukemia Research Foundatlon and grant CA62234 from the National Cancer Institute of America of the United States Public Health Service. We thank X. Qian Miao for expert technical assistance.

ASJC Scopus subject areas

Infectious Diseases
Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S1074-7613(95)80040-9

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title = "Integral membrane protein 2 of Epstein-barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases",

abstract = "An Epstein-Barr virus-encoded protein, LMP2, blocks the effects of surface immunoglobulin (slg) cross-linking on calcium mobilization and on lytic reactivation of EBV in latently infected and growth-transformed primary human B lymphocytes. In wild-type EBV-transformed cells, LMP2 is constitutively tyrosine phosphorylated and is associated with Lyn and Syk protein-tyrosine kinases (PTKs). Baseline Lyn PTK activity is substantially reduced, and slg cross-linking fails to activate Lyn, Syk, P13-K, PLCγ2, Vav, Shc, and MAPK. Syk, P13-K, PLCγ2, and Vav are constitutively tyrosine phosphorylated, and their tyrosine phosphorylation does not change following sIg cross-linking. In contrast, cross-linking sIg on cells transformed by LMP2 null mutant EBV recombinants triggers the same protein tyrosine kinase cascade as in noninfected B lymphocytes. These data are consistent with a model in which LMP2 is a constitutive dominant negative modulator of slg receptor signaling through its effects on Lyn, Syk, or regulators of these kinases.",

author = "Miller, {Cheryl L.} and Burkhardt, {Anne L.} and Lee, {Jennifer H.} and Becky Stealey and Richard Longnecker and Bolen, {Joseph B.} and Elliott Kieff",

note = "Funding Information: This work was supported by grant 47006 from the National Cancer Institute. R. L, is a Special Fellow of the Leukemia Society of America, and iS supported by the Leukemia Research Foundatlon and grant CA62234 from the National Cancer Institute of America of the United States Public Health Service. We thank X. Qian Miao for expert technical assistance.",

year = "1995",

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doi = "10.1016/S1074-7613(95)80040-9",

language = "English (US)",

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journal = "Immunity",

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AU - Miller, Cheryl L.

AU - Burkhardt, Anne L.

AU - Lee, Jennifer H.

AU - Stealey, Becky

AU - Longnecker, Richard

AU - Bolen, Joseph B.

AU - Kieff, Elliott

N1 - Funding Information: This work was supported by grant 47006 from the National Cancer Institute. R. L, is a Special Fellow of the Leukemia Society of America, and iS supported by the Leukemia Research Foundatlon and grant CA62234 from the National Cancer Institute of America of the United States Public Health Service. We thank X. Qian Miao for expert technical assistance.

PY - 1995/2

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N2 - An Epstein-Barr virus-encoded protein, LMP2, blocks the effects of surface immunoglobulin (slg) cross-linking on calcium mobilization and on lytic reactivation of EBV in latently infected and growth-transformed primary human B lymphocytes. In wild-type EBV-transformed cells, LMP2 is constitutively tyrosine phosphorylated and is associated with Lyn and Syk protein-tyrosine kinases (PTKs). Baseline Lyn PTK activity is substantially reduced, and slg cross-linking fails to activate Lyn, Syk, P13-K, PLCγ2, Vav, Shc, and MAPK. Syk, P13-K, PLCγ2, and Vav are constitutively tyrosine phosphorylated, and their tyrosine phosphorylation does not change following sIg cross-linking. In contrast, cross-linking sIg on cells transformed by LMP2 null mutant EBV recombinants triggers the same protein tyrosine kinase cascade as in noninfected B lymphocytes. These data are consistent with a model in which LMP2 is a constitutive dominant negative modulator of slg receptor signaling through its effects on Lyn, Syk, or regulators of these kinases.

AB - An Epstein-Barr virus-encoded protein, LMP2, blocks the effects of surface immunoglobulin (slg) cross-linking on calcium mobilization and on lytic reactivation of EBV in latently infected and growth-transformed primary human B lymphocytes. In wild-type EBV-transformed cells, LMP2 is constitutively tyrosine phosphorylated and is associated with Lyn and Syk protein-tyrosine kinases (PTKs). Baseline Lyn PTK activity is substantially reduced, and slg cross-linking fails to activate Lyn, Syk, P13-K, PLCγ2, Vav, Shc, and MAPK. Syk, P13-K, PLCγ2, and Vav are constitutively tyrosine phosphorylated, and their tyrosine phosphorylation does not change following sIg cross-linking. In contrast, cross-linking sIg on cells transformed by LMP2 null mutant EBV recombinants triggers the same protein tyrosine kinase cascade as in noninfected B lymphocytes. These data are consistent with a model in which LMP2 is a constitutive dominant negative modulator of slg receptor signaling through its effects on Lyn, Syk, or regulators of these kinases.

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Integral membrane protein 2 of Epstein-barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases

Abstract

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ASJC Scopus subject areas

UN SDGs

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