Related Experiment Video

Updated: Aug 8, 2026

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
10:21

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Published on: February 21, 2018

Distinct roles for leukemia inhibitory factor receptor alpha-chain and gp130 in cell type-specific signal

R Starr1, U Novak, T A Willson

  • 1Cooperative Research Centre for Cellular Growth Factors and the Walter and Eliza Hall Institute for Medical Research, Victoria 3050, Australia.

The Journal of Biological Chemistry
|August 8, 1997
PubMed

Insights

Leukemia inhibitory factor receptor (LIFR) signaling varies by cell type. The gp130 subunit mediates signals in multiple cells, while LIFR alpha primarily functions in embryonic stem cells, impacting differentiation and proliferation.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Receptor function

Background:

  • Leukemia inhibitory factor (LIF) elicits diverse cellular responses via its receptor (LIFR), a complex of LIFR alpha and gp130.
  • The distinct signaling capacities of LIFR alpha and gp130 cytoplasmic domains remain incompletely understood.

Purpose of the Study:

  • To investigate the individual signaling capabilities of the LIFR alpha and gp130 cytoplasmic domains.
  • To determine how these domains contribute to specific cellular responses like differentiation and proliferation in different cell types.

Main Methods:

  • Construction of chimeric receptors by fusing the granulocyte colony-stimulating factor receptor (GCSFR) extracellular domain to LIFR alpha or gp130 cytoplasmic and transmembrane regions.
  • Expression of chimeric receptors and full-length GCSFR in M1 myeloid leukemic cells, embryonic stem cells, and Ba/F3 cells.
  • Assessment of cellular responses including differentiation induction, differentiation inhibition, and cell proliferation.

Main Results:

  • The GCSFR-gp130 chimeric receptor mediated granulocyte colony-stimulating factor (GCSF)-induced signaling in all tested cell types (M1, embryonic stem cells, Ba/F3).
  • The GCSFR-LIFR alpha chimeric receptor showed functionality exclusively in embryonic stem cells, mediating GCSF-induced effects.
  • Differential signaling outputs were observed based on the receptor subunit and cell context.

Conclusions:

  • The gp130 cytoplasmic domain possesses broader signaling potential across different cell types compared to LIFR alpha.
  • The signaling capacity of LIFR alpha and gp130 is context-dependent, varying with cell type and the specific biological response.
  • These findings highlight distinct roles for receptor subunits in mediating context-specific cellular responses to LIF signaling.

More Related Videos

Identification of Functional Protein Regions Through Chimeric Protein Construction11:39

Identification of Functional Protein Regions Through Chimeric Protein Construction

Published on: January 8, 2019

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

Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: