Map kinase phosphatases (MKP's) are early responsive genes during induction of cerulein hyperstimulation pancreatitis.
Mitogen-activated protein kinase (MAPK) family members such as c-jun N-terminal kinase (JNK) may act as signal transducers early during pancreatitis development and evidence indicates that MAPK phosphatases (MKP) downregulate MAPK. We therefore investigated expression and regulation of pancreatic MKP in vivo. Pancreatic MKP mRNA levels were near or below the detection threshold in unstimulated animals. Cerulein hyperstimulation strongly induced MKP-1, MKP-3, and MKP-5 expression, peaking 30 to 60 min after treatment. Thus, MKP's clearly are early responsive genes during pancreatitis induction. Interestingly, inhibition of MKP-1 expression by Ro-31-8220 maximally induced activation of JNK but not of p38 and ERK in acutely isolated acini. These effects indicate that JNK may indeed be a preferred MKP-1 substrate in vivo.
Höfken
T
T
Department of Gastroenterology, University of Bern, Bern, Switzerland.
Keller
N
N
Fleischer
F
F
Göke
B
B
Wagner
A C
AC
D000208:Acute Disease; D000818:Animals; D018797:Cell Cycle Proteins; D002108:Ceruletide / Q000096:biosynthesis*; D054638:Dual Specificity Phosphatase 1; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010195:Pancreatitis / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D017874:Immediate-Early Proteins; D007211:Indoles; D012333:RNA, Messenger; D002108:Ceruletide; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases; C064758:Ro 31-8220