Related Experiment Video

Updated: May 15, 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

The role of endocytic pathways in TGF-β signaling

P Balogh1, S Katz, A L Kiss

  • 1Department of Human Morphology and Developmental Biology, Semmelweis University, Tűzoltó u. 58, Budapest, 1094, Hungary. balogh.petra@med.semmelweis-univ.hu

Pathology Oncology Research : POR
|January 1, 2013
PubMed

Insights

Transforming growth factor beta (TGF-β) signaling, crucial for cell processes and epithelial-mesenchymal transition (EMT), is regulated by endocytosis. Early endosomes manage TGF-β receptor signaling termination and degradation.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Biochemistry

Background:

  • The Transforming Growth Factor beta (TGF-β) superfamily regulates diverse cellular functions, including cell differentiation, migration, and adhesion.
  • TGF-β signaling is mediated by cell surface serine/threonine kinase receptors and can induce epithelial-mesenchymal transition (EMT) via Smad and MAPK pathways.
  • Type II EMT, associated with wound healing and fibrosis, can be triggered by growth factors like TGF-β and EGF.

Purpose of the Study:

  • To investigate the role of endocytic pathways in regulating TGF-β signaling.
  • To elucidate the function of early endosomes in both promoting and terminating TGF-β-induced cellular responses.
  • To understand how different internalization routes influence downstream signaling events.

Main Methods:

  • Analysis of endocytic routes involved in TGF-β ligand and receptor internalization.
  • Investigation of clathrin-coated vesicle and caveola-mediated endocytosis in TGF-β signaling.
  • Examination of the early endosome's role in managing TGF-β receptor trafficking and signaling outcomes.

Main Results:

  • Internalization via clathrin-coated vesicles enhances TGF-β signaling.
  • Caveola-mediated endocytosis is implicated in terminating TGF-β signaling, though mechanisms require further clarification.
  • Early endosomes are critical for both sustaining effective TGF-β signaling and directing internalized components towards degradation via multivesicular bodies and lysosomes.

Conclusions:

  • Endocytic pathways differentially regulate TGF-β signaling duration and intensity.
  • Early endosomes act as central hubs, balancing the promotion and termination of TGF-β-mediated cellular processes.
  • Understanding these endocytic mechanisms provides insights into TGF-β's role in development, disease, and potential therapeutic strategies.

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

TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing07:05

TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing

Published on: February 26, 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...
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...
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...
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...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...