Proteinase-activated receptors (PARs): activation of PAR1 and PAR2 by a proteolytic fragment of the neuronal growth associated protein B-50/GAP-43
| Autor: | Morley D Hollenberg, Mahmoud Saifeddine, Henk Zwiers |
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| Rok vydání: | 1999 |
| Předmět: | |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 78:81-85 |
| ISSN: | 1205-7541 0008-4212 |
| Popis: | The neuronal growth associated protein B-50/GAP-43 has been localized in synaptosomes both as an intact protein and as a partial proteolysis product (termed B-60) that has an N-terminal sequence SFRGHITR.... Because of the relationship of this amino acid sequence to those of the tethered ligand for the human proteinase activated receptors PAR1 (SFLLRN...) and PAR2 (SLIGKV...), we wished to determine whether the B-50/GAP-43-derived proteolytic fragment SFRGHITR (SFRB60) might function as a PAR-activating peptide (PAR-AP) to stimulate either PAR1 or PAR2. With the use of a newly developed PAR1/PAR2 receptor activation-desensitization assay, employing PAR1/PAR2-bearing cultured human embryonic kidney (HEK293) cells, we found that SFRB60 could activate both PAR1 and PAR2 so as to elevate intracellular calcium with EC50 values of approximately 200 and 50 µM, respectively. We also showed that trypsin can rapidly degrade B-50 to smaller fragments that would include the sequence SFRB60. Because PAR1 and PAR2 are present on neurones, our data raise the possibility that in certain circumstances in vivo, B-50/GAP-43 may play a signalling role by serving as a precursor for proteolytically generated PAR-activating peptides.Key words: proteinase-activated receptors, neurones, B-50/GAP-43, calcium signalling. |
| Databáze: | OpenAIRE |
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