Cyclic AMP inhibits the activity of c-Jun N-terminal kinase (JNKp46) but not JNKp55 and ERK2 in human helper T lymphocytes.
The cyclic AMP (cAMP) elevating agent PGE(2) and dibutyryl cyclic AMP (dBcAMP) affect T cell functions. Using human helper T cell clones, we examined effects of cAMP on c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), which are assumed to play a role in T cell regulation. When we analyzed the effects of dBcAMP on activities of mitogen-activated protein kinase (MAPK) family members ERK2, JNKp55 and JNKp46, dBcAMP did not inhibit the activities of ERK2 and JNKp55 induced by PMA/A23187 stimulation. JNKp46 activity was, however, inhibited by dBcAMP. JNK phosphorylates c-Jun on Ser-63 and Ser-73, the result being induction of its transcriptional activity. We found that dBcAMP inhibited the phosphorylation of c-Jun Ser-63 induced by PMA/A23187 stimulation. We suggest a different mechanism of regulation of JNKp55 and JNKp46 activities and that JNKp46 is a specific c-Jun kinase by which the activity of c-Jun is regulated in T lymphocytes.
Harada
Y
Y
Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Miyatake
S
S
Arai
K
K
Watanabe
S
S
D000906:Antibodies / Q000276:immunology; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008970:Molecular Weight; D004676:Myelin Basic Protein / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011233:Precipitin Tests; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000906:Antibodies; D004676:Myelin Basic Protein; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D010768:Phosphoserine; D000001:Calcimycin; D003994:Bucladesine; D000242:Cyclic AMP; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate