Faculty Collaboration Database

Induction of prostaglandin endoperoxide synthase 2 by mitogen-activated protein kinase cascades. Biochem J 2000 Dec 01;352 Pt 2(Pt 2):419-24

Date

11/22/2000

Pubmed ID

11085935

Pubmed Central ID

PMC1221473

Scopus ID

2-s2.0-0034534697 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

Prostaglandin endoperoxide synthase (PGHS) catalyses the rate-limiting step in the formation of prostaglandin and thromboxane eicosanoids from arachidonic acid released by phospholipase A(2). Two forms of PGHS exist, PGHS-1 and PGHS-2. PGHS-2, normally absent from cells, is rapidly expressed in response to a wide variety of stimuli and has been implicated in the pathogenesis of colon cancer and several inflammatory diseases. The three principal mitogen-activated protein kinase (MAPK) pathways are the extracellular signal-regulated protein kinase (ERK), the c-Jun N-terminal kinase (JNK) cascade and the p38-MAPK cascade. The present study was undertaken to investigate the putative involvement of the MAPK cascades in PGHS-2 induction. The potential role of ERK in PGHS-2 up-regulation was assessed by using cell lines expressing, both stably and after adenoviral infection, constitutively active forms of its upstream activator MAPK/ERK kinase (MEK1). The possible involvement of JNK and p38-MAPK in positively modulating PGHS-2 transcription was investigated by using adenovirus-mediated transfer of active forms of their respective specific upstream kinases, mitogen-activated protein kinase kinase (MKK) 7 and MKK3/MKK6. ERK activation promoted the induction of PGHS-2 mRNA and protein. Similarly, activation of JNK by Ad-MKK7D and p38-MAPK by Ad-MKK3bE/Ad-MKK6bE resulted in the increased expression of PGHS-2. These results provide evidence that activation of all three of the major mammalian MAPK leads to the induction of PGHS-2 mRNA and protein. Because PGHS-2 is up-regulated by a diverse range of stimuli, both mitogenic and stress-evoking, these results provide evidence that the convergence point of these stimuli could be the activation of one or more MAPK cascade(s).

Author List

McGinty A, Foschi M, Chang YW, Han J, Dunn MJ, Sorokin A

Author

Andrey Sorokin PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

3T3 Cells
Animals
Humans
Mice
Mitogen-Activated Protein Kinases
Prostaglandin-Endoperoxide Synthases
Up-Regulation