CYCLIC AMP-ELEVATING AGENTS NEGATIVELY REGULATE THE ACTIVATION OF P72(SYK) IN N-FORMYL-METHIONYL-LEUCYL-PHENYLALANINE RECEPTOR SIGNALING

Here we investigated the involvement of the non-receptor protein-tyros ine kinase p72(syk) in formyl methionyl-leucyl-phenylalanine (fMLP) re ceptor signaling. The activity of p72(syk) began to rise from 15 s and reached to maximum within 2-5 min after 5 mu M fMLP stimulation in po rcine polymorphonuclear neutrophils (PMNs). Cyclic AMP (cAMP)-elevatin g agents, prostaglandin E(2) (PGE(2)) and forskolin, or dibutyryl cAMP partially suppressed p72(Syk) activities stimulated by fMLP in PMNs. Pretreatment with an inhibitor of cAMP-dependent protein kinase abolis hed the suppression of the fMLP-induced p72(Syk) activation by these c AMP-elevating agents. It was also observed that cAMP-dependent protein kinase phosphorylates p72(Syk) on serine residues in vitro. These res ults indicate a possibility that cAMP-dependent protein kinase negativ ely regulates the activation of p72(syk) in fMLP-receptor signaling. ( C) 1995 Academic Press, Inc.