Abstract
Platelet factor 4 (PF‐4) blocks the binding of basic fibroblast growth factor (bFGF) to its receptor. In the present study, we constructed carboxyl‐terminal fragments, which represent the heparin‐binding region of the PF‐4 molecule, and examined whether these synthetic peptides retain the blocking effects on the receptor binding of bFGF. Synthetic peptides inhibited the receptor binding of bFGF. Furthermore, they inhibited the migration and tube formation of bovine capillary endothelial cells in culture (these phenomena are dependent on endogenous bFGF).
Keywords: Platelet factor 4, Heparin‐binding domain, Basic fibroblast growth factor, Receptor binding
Full Text
The Full Text of this article is available as a PDF (208.2 KB).
REFERENCES
- 1. ) Horton , J. E. , Harper , J. and Harper , E.Platelet factor 4 regulates osteoclastic bone resorption in vitro . Biochim. Biophys. Acta , 630 , 459 – 462 ( 1980. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Gewirtz , A. M. , Calabretta , B. , Rucinski , B. , Niewiarowski , S. and Xu , W. Y.Inhibition of human megakaryocytopoiesis in vitro by platelet factor 4 (PF4) and a synthetic COOH‐terminal PF4 peptide . J. Clin. Invest. , 83 , 1477 – 1486 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. ) Maione , T. E. , Gray , G. S. , Petro , J. , Hunt , A. J. , Donner , A. L. , Bauer , S. I. , Carson , H. F. and Sharpe , R. J.Inhibition of angiogenesis by recombinant human platelet factor‐4 and related peptides . Science , 247 , 77 – 79 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Sato , Y. , Abe , M. and Takaki , R.Platelet factor 4 blocks the binding of basic fibroblast growth factor to the receptor and inhibits the spontaneous migration of vascular endothelial cells . Biochem. Biophys. Res. Commun. , 172 , 595 – 600 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Sato , Y. , Shimada , T. and Takaki , R.Autocrinological role of basic fibroblast growth factor on tube formation of vascular endothelial cells in vitro . Biochem. Biophys. Res. Commun. , 180 , 1098 – 1102 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Sato , Y. and Rifkin , D. B.Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis . J. Cell Biol. , 107 , 1199 – 1205 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. ) Meienhofer , J. , Waki , M. , Heimer , E. P. , Lambros , T. J. , Makofske , R. C. and Chang , C.‐D.Solid phase synthesis without repetitive acidolysis. Preparation of leucyl‐alanylglycyl‐valine using 9‐fluorenyloxycarbonylamino acids . Int. J. Peptide Protein Res. , 13 , 35 – 42 ( 1979. ). [PubMed] [Google Scholar]
- 8. ) Waki , M. , Nakahara , T. and Ohno , M.FMOC‐based solid phase synthesis of peptide fragments of dopamine D2receptor and platelet factor‐4 using BOP reagent . In “ Peptide Chemistry 1990 ,” ed. Shimonishi Y. , pp. 95 – 98 ( 1991. ). Protein Research Foundation; , Osaka . [Google Scholar]
- 9. ) Rifkin , D. B , and Moscatelli , D.Recent developments in the cell biology of basic fibroblast growth factor . J. Cell Biol. , 109 , 1 – 6 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. ) Moscatelli , D.High and low affinity binding sites for basic fibroblast growth factor on cultured cells: absence of a role for low affinity binding in the stimulation of plasminogen activator production by bovine capillary endothelial cells . J. Cell Physiol. , 131 , 123 – 130 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Yayon , A. , Klagsbrun , M. , Esko , J. D. , Leder , P. and Ornitz , D. M.Cell surface, heparin‐like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor . Cell 64 , 841 – 848 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Rapraeger , A. C. , Krufka , A. and Olwin , B. B.Requirement of heparan sulfate for bFGF‐mediated fibroblast growth and myoblast differentiation . Science , 252 , 1705 – 1708 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Whitson , R. H. , Wong , W. L. and Itakura , K.Platelet factor 4 selectively inhibits binding of TGF‐β1 to the type 1 TGF‐β1 receptor . J. Cell. Biochem. , 47 , 31 – 42 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 14. ) McCaffrey , T. A. , Falcone , D. J. and Du , B.Transforming growth factor‐β1 is a heparin‐binding protein: identification of putative heparin‐binding regions and isolation of heparins with varying affinity for TGF‐β1 , J. Cell. Physiol. , 152 , 430 – 440 ( 1992. ). [DOI] [PubMed] [Google Scholar]