Related Experiment Video

Updated: Mar 12, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
11:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

12.6K

LMP1 signaling pathway activates IRF4 in latent EBV infection and a positive circuit between PI3K and Src is required

L Wang1,2, J Ren1,2, G Li1,2

  • 1Division of Infectious Diseases, Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.

Oncogene
|November 8, 2016
PubMed

Insights

Epstein-Barr virus protein LMP1 activates Interferon Regulatory Factor 4 (IRF4) via c-Src kinase signaling. This pathway, involving PI3K, is crucial for IRF4 activity in virus-transformed cells and may offer therapeutic targets.

Area of Science:

  • Molecular Biology
  • Virology
  • Immunology
  • Oncology

Background:

  • Interferon (IFN) regulatory factors (IRFs) are critical in immune responses and cancer development.
  • IRF4 activation by c-Src tyrosine phosphorylation is known in virus-transformed cells.
  • The specific signaling pathway leading to c-Src activation of IRF4 remains unclear.

Purpose of the Study:

  • To elucidate the intracellular signaling pathway responsible for Epstein-Barr virus (EBV) LMP1-mediated IRF4 activation.
  • To investigate the role of c-Src and phosphatidylinositol 3 kinase (PI3K) in this signaling cascade.
  • To identify potential therapeutic targets within the IRF4 regulatory network for hematological malignancies.

Main Methods:

  • Investigated the interaction between EBV latent membrane protein 1 (LMP1) and c-Src.
  • Utilized short hairpin RNAs (shRNAs) to deplete the PI3K subunit P85 and assess its role.
  • Employed the PI3K-specific inhibitor LY294002 to evaluate kinase activity and signaling pathways.

Main Results:

  • EBV LMP1 directly promotes IRF4 phosphorylation and enhances its transcriptional activity.
  • c-Src mediates LMP1-induced IRF4 activation, with LMP1 physically interacting with c-Src via the PI3K P85 subunit.
  • Src acts upstream of PI3K in activating both IRF4 and Akt; PI3K inhibition impairs Src activity.

Conclusions:

  • LMP1 signaling is the primary driver of IRF4 activation in EBV-transformed cells.
  • The identified signaling pathway involving LMP1, c-Src, PI3K, and IRF4 provides a deeper understanding of viral oncogenesis.
  • This IRF4 regulatory network represents a promising therapeutic target for treating specific hematological cancers.

More Related Videos

Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line09:14

Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line

Published on: September 28, 2022

4.7K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

890

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.1K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.6K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
15.5K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.7K
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
10.4K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.0K