Related Experiment Video

Updated: Jun 8, 2026

Bone Marrow-derived Macrophage Production
07:06

Bone Marrow-derived Macrophage Production

Published on: November 22, 2013

Induction of interleukin-6 expression by bone morphogenetic protein-6 in macrophages requires both SMAD and p38

Geun Taek Lee1, Seok Joo Kwon, Jae-Ho Lee

  • 1Dean and Betty Gallo Prostate Cancer Center and Section of Urologic Oncology, Division of Urology, Department of Surgery, the Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.

The Journal of Biological Chemistry
|October 5, 2010
PubMed

Insights

Bone morphogenetic protein-6 (BMP-6) activates macrophages and induces interleukin-6 (IL-6) expression. This involves BMP receptor type II, activin-like kinase-2, and cross-talk between Smad and p38 signaling pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Transforming growth factor-β (TGF-β) is a known modulator of immune responses.
  • Bone morphogenetic protein-6 (BMP-6) exhibits distinct functions compared to TGF-β, including macrophage activation.

Purpose of the Study:

  • To elucidate the signaling mechanism by which BMP-6 induces interleukin-6 (IL-6) expression in macrophages.
  • To identify the key molecular players and pathways involved in BMP-6-mediated IL-6 induction.

Main Methods:

  • Overexpression and knockdown experiments to assess the roles of BMP receptor type II and activin-like kinase-2.
  • Analysis of Smad and p38 signaling pathways activation.
  • Investigation of transcription factor involvement, including GATA4 and Smad 1/4.

Main Results:

  • BMP-6 treatment significantly increased IL-6 expression in macrophages.
  • BMP receptor type II and activin-like kinase-2 were essential for BMP-6-induced IL-6 production.
  • Both Smad and p38 signaling pathways were required for IL-6 induction.
  • Cross-talk between Smad and p38 pathways was observed at the level of GATA4 and Smad 1/4 transcription factors.

Conclusions:

  • A novel BMP-6 signaling pathway is identified, distinct from canonical TGF-β signaling.
  • This pathway involves the synergistic action of Smad and non-Smad (p38) signaling cascades.
  • The interaction between these pathways regulates the transcription of target genes like IL-6 in macrophages.

More Related Videos

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces07:55

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces

Published on: January 7, 2020

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

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...
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...
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 heterodimer of NF-κB...
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...
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...