Cyclic AMP-elevating agents negatively regulate the activation of p72syk in N-formyl-methionyl-leucyl-phenylalanine receptor signaling.
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.
Asahi
M
M
Department of Biochemistry, Fukui Medical School, Matsuoka, Japan.
Tanaka
Y
Y
Qin
S
S
Tsubokawa
M
M
Sada
K
K
Minami
Y
Y
Yamamura
H
H
D000595:Amino Acid Sequence; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D000072377:Syk Kinase
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D005576:Colforsin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003994:Bucladesine; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D015232:Dinoprostone