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-term inal kinase (JNK) may act as signal transducers early during pancreatitis d evelopment and evidence indicates that MAPK phosphatases (MKP) downregulate MAPK. We therefore investigated expression and regulation of pancreatic MK P in vivo. Pancreatic MRP mRNA levels were near or below the detection thre shold in unstimulated animals. Cerulein hyperstimulation strongly induced M KP-1, MKP-3, and MKP-5 expression, peaking 30 to 60 min after treatment. Th us, MKP's clearly are early responsive genes during pancreatitis induction. Interestingly, inhibition of MKP-1 expression by Ro-31-8220 maximally indu ced activation of JNK but not of p38 and ERK in acutely isolated acini. The se effects indicate that JNK may indeed be a preferred MKP-1 substrate in v ivo, (C) 2000 Academic Press.