Related Experiment Video

Updated: Jun 19, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

Involvement of the c-jun N-terminal kinases JNK1 and JNK2 in complement-mediated cell death

Dana Gancz1, Natalie Donin, Zvi Fishelson

  • 1Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

Molecular Immunology
|October 30, 2009
PubMed

Insights

The JNK pathway, particularly JNK2, mediates cell death signals initiated by the complement attack complex C5b-9, impacting complement-associated diseases and cancer therapies.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The complement membrane attack complex (C5b-9) triggers cell death and survival signals.
  • These signals are crucial in complement-associated diseases and antibody-based cancer therapies.
  • The role of JNK (c-Jun N-terminal kinase) in C5b-9-induced cell death remains unclear.

Purpose of the Study:

  • To investigate the involvement of JNK mitogen-activated protein kinase in C5b-9-induced cell lysis.
  • To determine the specific roles of JNK1 and JNK2 in regulating necrotic cell death.
  • To elucidate the signaling pathway downstream of C5b-9 leading to cell death.

Main Methods:

  • Studied JNK activation and cell lysis in response to C5b-9 in mouse fibroblasts and human cell lines (K562, HeLa, 293T).
  • Utilized JNK inhibitors, knockout (KO) cells deficient in JNK1 or JNK2, and RNA interference for gene silencing.
  • Investigated complement component deposition (C3, C5b-9) and employed phosphotyrosine phosphatase inhibitor (phenylarsine oxide) and Bid-deficient cells.

Main Results:

  • C5b-9 induced significant JNK activation, more so than C5b-8.
  • JNK inhibition or deficiency reduced sensitivity to complement-mediated lysis and decreased C3/C5b-9 deposition.
  • JNK1 and JNK2 silencing decreased cell lysis; JNK2 reconstitution/overexpression enhanced lysis and deposition.
  • Phenylarsine oxide increased JNK activation and JNK-dependent cell death, implicating Bid in the JNK lytic pathway.

Conclusions:

  • Complement C5b-9 induces necrotic cell death through both JNK/Bid-dependent and JNK-independent pathways.
  • Both JNK1 and JNK2 contribute to C5b-9-mediated cell death, with JNK2 acting as the primary signal transducer.
  • Understanding this pathway offers insights into complement-associated diseases and cancer therapy strategies.

More Related Videos

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Related Concept Videos

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...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...