Related Experiment Video

Updated: May 3, 2026

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
08:15

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System

Published on: April 11, 2025

1.1K

The Gβγ-Src signaling pathway regulates TNF-induced necroptosis via control of necrosome translocation

Lisheng Li1, Wanze Chen1, Yaoji Liang1

  • 1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China.

Cell Research
|February 12, 2014
PubMed

Insights

Tumor necrosis factor α (TNF)-induced necroptosis relies on G protein signaling. Disruption of guanine nucleotide-binding protein γ 10 (Gγ10) blocks TNF-induced necroptosis by impairing necrosome trafficking.

Area of Science:

  • Cellular biology
  • Molecular signaling pathways

Background:

  • Necrosomes are crucial for tumor necrosis factor α (TNF)-induced programmed necrosis (necroptosis).
  • The precise molecular mechanisms governing necroptosis remain largely undefined.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying TNF-induced necroptosis.
  • To identify novel components involved in the necroptosis signaling pathway.

Main Methods:

  • Isolation and characterization of a TNF-resistant L929 mutant cell line.
  • Gene disruption analysis to identify the responsible gene (guanine nucleotide-binding protein γ 10 - Gγ10).
  • Investigation of signaling pathways including Src, NF-κB, and MAPKs; assessment of necrosome formation and trafficking.

Main Results:

  • Disruption of the Gγ10 gene confers resistance to TNF-induced necroptosis.
  • Gγ10 interacts with Gβ2 and functions upstream of Src activation in this pathway.
  • Gγ10 is essential for the trafficking of necrosomes to their functional site, independent of RIP1/RIP3 kinase activity and necrosome formation itself.

Conclusions:

  • The Gβ2γ10-Src signaling pathway is a critical, previously unrecognized component of TNF-induced necroptosis.
  • Gγ10's role in necrosome trafficking is essential for the execution of necroptosis, highlighting a new regulatory mechanism beyond kinase activity and complex formation.

More Related Videos

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay05:52

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay

Published on: May 12, 2023

2.1K
Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

7.9K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.6K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
5.2K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
15.3K
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...
6.2K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K