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Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta
José G Abreu1, Nan I Ketpura, Bruno Reversade
1Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Riverside, 9095-1662, USA.
Nature Cell Biology
|July 23, 2002
Summary
Connective-tissue growth factor (CTGF) directly binds bone morphogenetic protein 4 (BMP4) and transforming growth factor-beta 1 (TGF-beta 1). CTGF inhibits BMP4 signaling while enhancing TGF-beta 1 signaling through extracellular binding.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Connective-tissue growth factor (CTGF) is a secreted protein involved in angiogenesis, skeletogenesis, and wound healing.
- CTGF belongs to the CCN family of secreted proteins, but its molecular mechanism in cell signaling remains unclear.
- CTGF possesses a cysteine-rich (CR) domain, potentially involved in binding growth factors like BMP and TGF-beta.
Purpose of the Study:
- To investigate the molecular mechanism of CTGF in regulating cell signaling.
- To determine if CTGF directly binds BMP4 and TGF-beta 1.
- To elucidate how CTGF binding affects BMP and TGF-beta signaling pathways.
Main Methods:
- Direct binding assays to assess CTGF interaction with BMP4 and TGF-beta 1.
- Analysis of CTGF's CR domain for growth factor binding.
- Functional assays to evaluate the impact of CTGF on BMP and TGF-beta receptor binding and signaling.
Main Results:
- CTGF directly binds to both BMP4 and TGF-beta 1 via its CR domain.
- CTGF antagonizes BMP4 activity by blocking its binding to BMP receptors.
- CTGF enhances TGF-beta 1 binding to its receptors, thereby activating TGF-beta signaling.
Conclusions:
- CTGF acts as a direct modulator of BMP and TGF-beta signaling pathways.
- The CR domain of CTGF is crucial for its interaction with BMP4 and TGF-beta 1.
- CTGF's differential regulation of BMP and TGF-beta signaling occurs through extracellular binding, impacting key cellular processes.