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PMID: 10357818 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Latent membrane protein 1 of Epstein-Barr virus interacts with JAK3 and activates STAT proteins.

The EMBO journal ·Vol. 18 ·No. 11 ·1999-06-01 ·Pages 3064-73

Gires O, Kohlhuber F, Kilger E, Baumann M, Kieser A, Kaiser C, Zeidler R, Scheffer B, Ueffing M, Hammerschmidt W

Abstract

Latent membrane protein 1 (LMP1) acts like a permanently activated receptor of the tumor necrosis factor (TNF)-receptor superfamily and is absolutely required for B cell immortalization by Epstein-Barr virus. Molecular and biochemical approaches demonstrated that LMP1 usurps cellular signaling pathways resulting in the induction of NF-kappaB and AP-1 via two C-terminal activating regions. We demonstrate here that a third region encompassing a proline rich sequence within the 33 bp repetitive stretch of LMP1's C-terminus is required for the activation of Janus kinase 3 (JAK3). The interaction of LMP1 and JAK3 leads to the enhanced tyrosine auto/transphosphorylation of JAK3 within minutes after crosslinking of a conditional NGF-R:LMP1 chimera and is a prerequisite for the activation of STAT transcription factors. These results reveal a novel activating region in the LMP1 C-terminus and identify the JAK/STAT pathway as a target of this viral integral membrane protein in B cells.

MeSH Terms
Amino Acid Sequence Animals B-Lymphocytes/enzymology,metabolism Cell Line Consensus Sequence/genetics DNA/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Enzyme Activation Herpesvirus 4, Human/genetics,metabolism Humans Janus Kinase 3 Mice Molecular Sequence Data Phosphorylation Phosphotyrosine/metabolism Proline/genetics,metabolism Protein Binding Protein-Tyrosine Kinases/genetics,metabolism Receptors, Nerve Growth Factor/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Repetitive Sequences, Amino Acid STAT1 Transcription Factor Sequence Deletion Signal Transduction Trans-Activators/genetics,metabolism Viral Matrix Proteins/chemistry,genetics,metabolism
Chemicals
DNA-Binding Proteins EBV-associated membrane antigen, Epstein-Barr virus Receptors, Nerve Growth Factor Recombinant Fusion Proteins STAT1 Transcription Factor STAT1 protein, human Stat1 protein, mouse Trans-Activators Viral Matrix Proteins Phosphotyrosine DNA Proline Protein-Tyrosine Kinases JAK3 protein, human Jak3 protein, mouse Janus Kinase 3
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Gires O
GSF-National Research Center for Environment and Health, Marchioninistrasse 25, D-81377 München, Germany.
Kohlhuber F
Kilger E
Baumann M
Kieser A
Kaiser C
Zeidler R
Scheffer B
Ueffing M
Hammerschmidt W
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/18.11.3064
Published
1999-06-01
Pages
3064-73
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171388
Subset
IM
Grants
NCI NIH HHS · CA70723 · United States
External Links
PubMed source DOI: 10.1093/emboj/18.11.3064 PMC Full Text View journal details
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