Jun and MAP kinases are activated by cholecystokinin in the pancreatic carcinoma cell line KP-1N.
Growth of the human pancreatic carcinoma cell line KP-1N was stimulated with cholecystokinin (CCK)-8. A 40% increase in cell numbers was observed in the presence of 10(-10) MCCK-8 and this increase was inhibited by the addition of 25 microM CCK-A receptor antagonist (CR1505). The binding affinity of CCK-8 to KP-1N cells was 21-fold higher than that of gastrin 17-I. No significant increase in intracellular Ca2+ concentration was found upon stimulation with CCK-8. Components of signal transduction pathways that were activated in KP-1N cells after stimulation with CCK-8 were studied. CCK-8 stimulated tyrosine phosphorylation of a mitogen-activated protein kinase (MAPK) of approximately 42 kDa (p42map). c-Jun amino-terminal kinases (JNKs) of 46 kDa (p46jnk) and 55 kDa (p55jnk) were also activated by CCK-8 and increased the phosphorylation of c-Jun. CCK-8 at 10(-7) M induced 1.5-fold increases in the phosphorylation of MAPK and of c-Jun by JNKs, respectively. These results suggest that cell proliferation stimulated with CCK-8 in KP-1N cells may be mediated by signal transduction cascades leading to activation of JNKs and MAPKs.
Tateishi
K
K
Department of Biochemistry, School of Medicine, Fukuoka University, Japan.
Funakoshi
A
A
Misumi
Y
Y
Matsuoka
Y
Y
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D012844:Sincalide / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D012844:Sincalide