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Regulation of TGFβ and related signals by precursor processing

Daniel B Constam1

  • 1Ecole Polytechnique Fédérale de Lausanne (EPFL), Bâtiment SV ISREC, Station 19, CH-1015 Lausanne, Switzerland.

Seminars in Cell & Developmental Biology
|February 11, 2014
PubMed

Insights

Transforming growth factor beta (TGFβ) precursor processing by proprotein convertases (PCs) is crucial for cell signaling. This review explores PC regulation of TGFβ maturation and its roles in development and disease.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Transforming growth factor beta (TGFβ) cytokines regulate fundamental cellular processes like proliferation, differentiation, migration, and survival in multicellular organisms.
  • Signal transduction pathways involve receptor kinases and Smad transcription factors to control gene expression.
  • Proprotein convertases (PCs) are proteases that process TGFβ family ligands, influencing signaling gradients and cell fate determination.

Purpose of the Study:

  • To review the proteolytic processing of TGFβ and related precursors.
  • To summarize the spatiotemporal regulation of this processing by PCs during development and disease.
  • To highlight the multifaceted roles of proteolytic maturation beyond receptor binding.

Main Methods:

  • Literature review of studies on TGFβ precursor processing.
  • Analysis of the role of proprotein convertases (PCs) in TGFβ maturation.
  • Examination of the impact of proteolytic processing on TGFβ signaling in development and disease contexts.

Main Results:

  • Proteolytic processing by PCs is essential for generating mature TGFβ ligands.
  • PCs regulate the concentration-dependent signaling gradients of BMP and Nodal subgroups.
  • Evidence suggests precursor processing has functions beyond unmasking receptor binding epitopes.

Conclusions:

  • Proteolytic maturation by PCs is a critical regulatory step in TGFβ signaling.
  • Dysregulation of PC-mediated processing contributes to developmental abnormalities and diseases like cancer.
  • Future research should investigate the impact of proteolytic maturation on protein localization, trafficking, and turnover.
Keywords:
BMPConvertasesDPP precursorFurinLatencyMorphogen gradientsNodal signalingProprotein processingProtein sorting and trafficking

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