A protein kinase involved in the regulation of inflammatory cytokine biosynthesis.
Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds. Using radiolabelled and radio-photoaffinity-labelled chemical probes, the target of these compounds was identified as a pair of closely related mitogen-activated protein kinase homologues, termed CSBPs. Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production.
Lee
J C
JC
Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406.
Laydon
J T
JT
McDonnell
P C
PC
Gallagher
T F
TF
Kumar
S
S
Green
D
D
McNulty
D
D
Blumenthal
M J
MJ
Heys
J R
JR
Landvatter
S W
SW
Strickler
J E
JE
McLaughlin
M M
MM
Siemens
I R
IR
Fisher
S M
SM
Livi
G P
GP
White
J R
JR
Adams
J L
JL
Young
P R
PR
D000595:Amino Acid Sequence; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018076:DNA, Complementary; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018836:Inflammation Mediators; D007375:Interleukin-1 / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments; D011725:Pyridines / Q000494:pharmacology; D011869:Radioligand Assay; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases
D016207:Cytokines; D018076:DNA, Complementary; D007093:Imidazoles; D018836:Inflammation Mediators; D007375:Interleukin-1; D010446:Peptide Fragments; D011725:Pyridines; D011994:Recombinant Proteins; C090943:SB 206718; D014409:Tumor Necrosis Factor-alpha; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole