Thrombin receptor-derived peptide SFLLRNP (one-letter amino acid code) which corresponds to the N-terminal heptapeptide of tethered ligand is able to activate thrombin receptor and to stimulate the phosphoinositide (PI) turnover. The replacement of Phe-2 by Ala eliminated this activity completely, showing the crucial role of the Phephenyl group in receptor activation. It was found that substitution of parafluorophenylalanine ((p- F)Phe) for Phe-2 enhanced several times the PI-turnover activity of SFLLRNP. This is the first example to date of a substitution with one order of magnitude greater increase in receptor activation. The Phe-2/Tyr substitution diminished the activity drastically (almost 2% of SFLLRNP), indicating the importance of hydrophobicity of Phe2-phenyl. The Phe-2/Leu substitution, however, diminished also the activity (less than 2% of SFLLRNP). These results suggested that highly specific hydrophobic interaction exists between Phe-2 of the tethered ligand and its binding site in thrombin receptor.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - Jun 15 1993|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology