Inhibition of protein kinase C by a peptide conjugate homologous to a domain of the retroviral protein p15E
| Autor: | R A Gottlieb, E S Kleinerman, C A O'Brian, S Tsujimoto, G J Cianciolo, W J Lennarz |
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| Rok vydání: | 1990 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 145:2566-2570 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.145.8.2566 |
| Popis: | Retroviral infection is associated with immunosuppression, which has been shown to be due, in part, to the action of the envelope protein p15E. We studied a synthetic peptide (CKS-17) homologous to a highly conserved domain of the retroviral envelope protein p15E, which, when conjugated to BSA (CKS-17-BSA), can inhibit IL-1- and phorbol ester-mediated responses in cultured murine thymoma cells, and Ca2(+)- and phosphatidylserine-dependent protein kinase C (PKC) activity of cell homogenates. We characterized the mechanism of inhibition of PKC by the peptide. Using PKC purified from rat brain we found that CKS-17-BSA inhibited PKC-catalyzed Ca2(+)- and phosphatidylserine-dependent histone phosphorylation with an estimated ID50 of 4 microM. CKS-17-BSA did not inhibit the catalytic subunit of cAMP-dependent protein kinase. CKS-17-BSA also inhibited the Ca2(+)- and PS-independent activity of a catalytic fragment of PKC that was generated by limited trypsin treatment. However, CKS-17-BSA did not act as a competitive inhibitor of PKC with respect to ATP or phosphoacceptor substrate, despite the similarity between the CKS-17 sequence and substrates and pseudosubstrates of PKC. We conclude that this peptide homologue of a retroviral envelope protein has a novel mechanism of inhibition of PKC. |
| Databáze: | OpenAIRE |
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