Cyclic AMP-elevating agents negatively regulate the activation of p72syk in N-formyl-methionyl-leucyl-phenylalanine receptor signaling

Abstract

Here we investigated the involvement of the non-receptor protein-tyrosine kinase p72syk in formyl methionyl-leucyl-phenylalanine (fMLP) receptor signaling. The activity of p72syk began to rise from 15 s and reached to maximum within 2-5 min after 5 microM fMLP stimulation in porcine polymorphonuclear neutrophils (PMNs). Cyclic AMP (cAMP)-elevating agents, prostaglandin E2 (PGE2) and forskolin, or dibutyryl cAMP partially suppressed p72syk activities stimulated by fMLP in PMNs. Pretreatment with an inhibitor of cAMP-dependent protein kinase abolished the suppression of the fMLP-induced p72syk activation by these cAMP-elevating agents. It was also observed that cAMP-dependent protein kinase phosphorylates p72syk on serine residues in vitro. These results indicate a possibility that cAMP-dependent protein kinase negatively regulates the activation of p72syk in fMLP-receptor signaling.