Related Experiment Video

Updated: Aug 3, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

Downregulation of IL-6-induced STAT3 tyrosine phosphorylation by TGF-beta1 is mediated by caspase-dependent and

A T J Wierenga1, J J Schuringa, B J L Eggen

  • 1University Hospital Groningen, Dept of Hematology, Groningen, The Netherlands.

Leukemia
|April 18, 2002
PubMed

Insights

Transforming growth factor-beta1 (TGF-beta1) can reduce interleukin-6 (IL-6)-induced STAT3 phosphorylation in acute myeloid leukemia (AML) cells by degrading JAK kinases. This cross-talk involves apoptosis and caspase activity.

Area of Science:

  • Hematology
  • Molecular Biology
  • Cell Signaling

Background:

  • Interleukin-6 (IL-6) and Transforming Growth Factor-beta1 (TGF-beta1) are key cytokines in acute myeloid leukemia (AML) pathogenesis.
  • Understanding cross-talk between IL-6 and TGF-beta1 pathways is crucial for AML treatment strategies.

Purpose of the Study:

  • To investigate the cross-talk between IL-6 and TGF-beta1 signaling pathways in AML blast cells.
  • To determine the effect of TGF-beta1 pretreatment on IL-6-induced STAT3 tyrosine phosphorylation.

Main Methods:

  • AML blast cells were pretreated with TGF-beta1 and then stimulated with IL-6.
  • STAT3 tyrosine phosphorylation, SMAD3 translocation, JAK/Tyk kinase activity, and ERK phosphorylation were assessed.
  • Apoptosis was induced using VP16, and caspase activity was inhibited using Z-VAD-fmk.

Main Results:

  • TGF-beta1 pretreatment reduced IL-6-induced STAT3 tyrosine phosphorylation in 10% of AML cases.
  • This reduction was linked to JAK1/2 and Tyk2 degradation and apoptosis, but not ERK changes.
  • VP16-induced apoptosis mimicked JAK kinase degradation and STAT3 phosphorylation reduction.
  • Caspase inhibition partially rescued JAK degradation but not the TGF-beta1-mediated attenuation of STAT3 phosphorylation.

Conclusions:

  • TGF-beta1 can attenuate IL-6-induced STAT3 signaling in a subset of AML cases.
  • JAK kinase degradation and apoptosis play a role in this cross-talk.
  • Caspase-independent mechanisms may also contribute to TGF-beta1's effect on STAT3 phosphorylation.

More Related Videos

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Related Concept Videos

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 activation may...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
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...
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...
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 are of three kinds RI, RII, and RIII. The RI...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...