Staurosporine and herbimycin A augment agonist-induced elevation of cAMP in Jurkat T-lymphoblasts.
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.
Buc
H A
HA
Laboratoire de Biochimie Métabolique et Pharmacologique, INSERM U75, Paris, France.
Moncion
A
A
Pérignon
J L
JL
D000249:Adenosine Monophosphate / Q000032:analysis*; D016227:Benzoquinones; D002460:Cell Line; D006801:Humans; D047029:Lactams, Macrocyclic; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D019311:Staurosporine / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000737:chemistry*
D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D047428:Protein Kinase Inhibitors; D011809:Quinones; D017828:Rifabutin; D000249:Adenosine Monophosphate; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine