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Thrombin inactivates acidic fibroblast growth factor but not basic fibroblast growth factor
1Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, Massachusetts.
Biochemistry
|April 5, 1988
Summary
Thrombin cleaves acidic fibroblast growth factor (aFGF), reducing its mitogenic and heparin-binding abilities. This cleavage reveals a functional role for aFGF
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Signaling
Background:
- Acidic fibroblast growth factor (aFGF) is a mitogen crucial for cell growth.
- Thrombin is a key enzyme in blood coagulation.
- Heparin binding is essential for growth factor activity.
Purpose of the Study:
- To investigate the effect of thrombin on acidic fibroblast growth factor (aFGF).
- To determine the functional consequences of aFGF cleavage by thrombin.
- To explore the role of aFGF fragments in biological processes.
Main Methods:
- Incubation of aFGF with varying concentrations of thrombin.
- Analysis of aFGF cleavage products using molecular weight determination.
- Assessment of mitogenic activity and heparin-binding affinity of aFGF and its fragments.
- Identification of thrombin cleavage sites using peptide mapping.
Main Results:
- Thrombin cleaves aFGF, generating a 14 kDa fragment with reduced heparin affinity and mitogenic potency.
- A specific 18-amino acid peptide (aFGF(123-140)) is produced, indicating cleavage at the Arg-122/Thr-123 bond.
- Heparin and specific thrombin inhibitors block aFGF cleavage.
- Basic fibroblast growth factor is resistant to thrombin cleavage under similar conditions.
Conclusions:
- The C-terminal region of aFGF is critical for its mitogenic activity and heparin binding.
- Thrombin-mediated cleavage of aFGF generates fragments with altered biological functions.
- This study suggests a novel role for heparin-binding growth factors and their fragments in thrombin-associated physiological and pathological conditions.