Related Experiment Video

Updated: Jun 14, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

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

Published on: October 27, 2020

Interleukin-1R-associated kinase 2 is a novel modulator of the transforming growth factor beta signaling cascade

Jasper Mullenders1, Armida W M Fabius, Miranda M W van Dongen

  • 1Division of Molecular Carcinogenesis, Center for Biomedical Genetics and Cancer Genomics Center, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Molecular Cancer Research : MCR
|March 25, 2010
PubMed

Insights

Interleukin-1R-associated kinase 2 (IRAK2) is identified as a novel component of the transforming growth factor beta (TGFbeta) pathway. Its suppression impairs TGFbeta signaling and overrides cell cycle arrest, highlighting its critical role.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Cancer Research

Background:

  • The transforming growth factor beta (TGFbeta) pathway regulates crucial cellular processes like cell cycle and migration.
  • TGFbeta signaling has a dual role in cancer, acting as a tumor suppressor in early stages and promoting invasion in later stages.
  • Identifying novel regulators of TGFbeta signaling is critical for understanding its complex roles.

Purpose of the Study:

  • To identify novel genes involved in transforming growth factor beta (TGFbeta) pathway signaling.
  • To elucidate the function of previously unlinked genes in TGFbeta-mediated cellular responses.

Main Methods:

  • A functional genetic loss-of-function screen using a small interfering RNA library targeting 700 kinases and kinase-related genes.
  • Utilized a TGFbeta-responsive reporter assay to identify genes modulating pathway activity.
  • Investigated the effect of gene knockdown on TGFbeta target gene response, SMAD2 phosphorylation, and nuclear accumulation.

Main Results:

  • Identified several genes, including known TGFbeta receptors, that upon knockdown repressed the reporter signal.
  • Discovered novel genes not previously linked to TGFbeta signaling.
  • Knockdown of interleukin-1R-associated kinase 2 (IRAK2) impaired TGFbeta target gene response, reduced SMAD2 phosphorylation and nuclear accumulation, and partially overrode TGFbeta-induced cell cycle arrest.

Conclusions:

  • Interleukin-1R-associated kinase 2 (IRAK2) is a novel and critical component of the transforming growth factor beta (TGFbeta) signaling pathway.
  • IRAK2 plays a significant role in mediating TGFbeta's effects on gene expression, SMAD2 activation, and cell cycle regulation.
  • These findings provide new insights into the molecular mechanisms governing TGFbeta signaling and its implications in cellular processes and cancer.

More Related Videos

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

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Related Concept Videos

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...
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...
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...
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...
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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...