Related Experiment Video

Updated: Oct 23, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Transforming growth factor beta1 rescues serum deprivation-induced apoptosis via the mitogen-activated protein kinase

B Y Chin1, I Petrache, A M Choi

  • 1Toxicological Sciences, Environmental Health Sciences, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.

The Journal of Biological Chemistry
|April 10, 1999
PubMed

Insights

Transforming growth factor beta1 (TGF-beta1) prevents apoptosis in macrophages, acting as a cell survival factor. This protective effect is mediated through TGF-beta receptor II (TbetaR-II) and downstream mitogen-activated protein kinase (MAPK) signaling pathways.

Area of Science:

  • Cellular biology
  • Immunology
  • Molecular signaling

Background:

  • Cell death and survival are critical in development and disease.
  • Transforming growth factor beta1 (TGF-beta1) is a cytokine influencing cell growth and death.
  • Understanding TGF-beta1's role in apoptosis is key to elucidating cell fate mechanisms.

Purpose of the Study:

  • To investigate the role of TGF-beta1 in regulating apoptosis in macrophages.
  • To identify the specific signaling pathways involved in TGF-beta1's effect on cell survival.

Main Methods:

  • Utilized murine macrophages (RAW 264.7) subjected to serum deprivation.
  • Employed dominant-negative inhibition of TGF-beta1 receptor II (TbetaR-II) and mitogen-activated protein kinase (MAPK) pathways.
  • Assessed apoptosis using DNA laddering assays and measured extracellular signal-regulated kinase (ERK) activity.

Main Results:

  • TGF-beta1 inhibited apoptosis in serum-deprived macrophages.
  • This protective effect was abolished by dominant-negative TbetaR-II.
  • TGF-beta1 induced ERK activity, and inhibiting MAPK signaling blocked its anti-apoptotic function.

Conclusions:

  • TGF-beta1 acts as an inhibitor of apoptosis in cultured macrophages.
  • Cell survival mediated by TGF-beta1 involves TbetaR-II and downstream MAPK signaling.
  • These findings highlight TGF-beta1's role as a crucial cell survival factor in macrophages.

More Related Videos

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

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

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...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
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...