Related Experiment Video

Updated: May 28, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

How do pleiotropic kinase hubs mediate specific signaling by TNFR superfamily members?

Bärbel Schröfelbauer1, Alexander Hoffmann

  • 1Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0375, USA. bschroefelbauer@ucsd.edu

Immunological Reviews
|October 25, 2011
PubMed

Insights

Tumor necrosis factor receptor (TNFR) superfamily signaling relies on specific kinases to control diverse cellular responses like survival and immunity. This review explores how scaffolding, combinatorial signaling, and temporal control ensure specificity in these complex pathways.

Area of Science:

  • Cellular biology
  • Molecular signaling
  • Immunology

Background:

  • Tumor necrosis factor receptor (TNFR) superfamily members are crucial for diverse cellular processes including cell death, survival, differentiation, proliferation, and immune regulation.
  • A limited set of pleiotropic kinases regulate these varied physiological responses.
  • The involvement of shared signaling molecules in transducing signals from TNFR superfamily members raises questions about specificity determination.

Purpose of the Study:

  • To review regulatory strategies that determine signaling specificity within the TNFR superfamily.
  • To discuss how scaffolding, combinatorial signaling, and temporal control contribute to specificity.

Main Methods:

  • Literature review of signaling mechanisms in TNFR superfamily.
  • Analysis of regulatory strategies impacting kinase specificity.
  • Discussion of temporal control in signal transduction.

Main Results:

  • Scaffolding can control kinase specificity.
  • Combinatorial use of signal transducers contributes to specificity.
  • Temporal control of signaling is a key regulatory strategy.

Conclusions:

  • Specificity in TNFR superfamily signaling is achieved through intricate regulatory mechanisms.
  • Understanding these strategies is vital for comprehending cellular responses to TNFR signaling.
  • Further research into these mechanisms can inform therapeutic interventions.

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Related Concept Videos

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...
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...
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 the...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
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...
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 rapamycin-insensitive companion...