Staurosporine and herbimycin A augment agonist-induced elevation of cAMP in Jurkat T-lymphoblasts.

Autor: Buc HA; Laboratoire de Biochimie Métabolique et Pharmacologique, INSERM U75, Paris, France., Moncion A, Pérignon JL
Jazyk: angličtina
Zdroj: International journal of immunopharmacology [Int J Immunopharmacol] 1996 Feb; Vol. 18 (2), pp. 135-9.
DOI: 10.1016/0192-0561(95)00116-6
Abstrakt: Cross-talk between signalling pathways appears to play an important role in T-lymphocyte activation. In the present work, we have studied the effects of different inhibitors of protein tyrosine kinases or protein serine/ threonine kinases on the agonist-induced cAMP accumulation in the human T-lymphoblast cell line Jurkat. Staurosporine, a potent but nonspecific inhibitor of protein kinases, produced a ten-fold enhancement of the response to PGE2. No significant effect was obtained with two specific protein kinase C inhibitors (GF 109203X and H7), whereas herbimycin A, a specific protein tyrosine kinase inhibitor, markedly enhanced the PGE2-induced cAMP accumulation: its effect was approximately 60% that of staurosporine. It was confirmed that both staurosporine and herbimycin A inhibited by more than 90% the release of IP3 induced by ligation of the T-cell receptor, a known protein tyrosine kinase-dependent mechanism. To our knowledge, this study provides the first indication of a protein tyrosine kinase-mediated inhibition of agonist-induced cAMP accumulation. The possible targets of this inhibition are discussed.
Databáze: MEDLINE