|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
21
|
|
pubmed:dateCreated |
1998-6-25
|
|
pubmed:abstractText |
The mitogen-activated protein kinase (MAPK) cascade is believed to function as an important regulator of prostaglandin biosynthesis. Previously we reported that interleukin-1beta induces activation of JNK/SAPK and p38 MAPK with concomitant up-regulation of cyclooxygenase (Cox)-2 expression and prostaglandin E2 (PGE2) synthesis. Our experiments demonstrate that overexpression of DeltaMEKK1 (a constitutively active truncation mutant of MEKK1 containing the C-terminal 324 amino acids) increases Cox-2 expression and PGE2 production which is completely blocked by SC68376, a pharmacologic inhibitor of p38 MAPK. DeltaMEKK1 overexpression results in activation of both c-Jun N-terminal kinases/extracellular signal-regulated kinases (JNK/SAPK) and p38 MAPK. Furthermore, activation of MEKK1 increases SEK1/MKK4 but not MKK3 or MKK6 activity. These findings suggest that MEKK1 --> SEK1/MKK4 may function as an upstream kinase capable of activating both p38 MAPK and JNK/SAPK with subsequent induction of Cox-2 expression and PGE2 production. We also found that overexpression of the constitutively active form of SEK1 (SEK1-ED) increases both p38 MAPK and JNK/SAPK phosphorylation, and increases PGE2 production and Cox-2 expression. By comparison, overexpression of the dominant negative form of SEK1 (SEK1-AL) decreases the phosphorylation of both p38 MAPK and JNK/SAPK and reduces Cox-2 expression. Together, this data suggests a potential role for the MEKK1 --> SEK1/MKK4 --> p38 MAPK -->--> Cox-2 cascade linking members of the MAPK pathway with prostaglandin biosynthesis.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Map2k4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Map3k1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
22
|
|
pubmed:volume |
273
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
12901-8
|
|
pubmed:dateRevised |
2011-11-2
|
|
pubmed:meshHeading |
pubmed-meshheading:9582321-3T3 Cells,
pubmed-meshheading:9582321-Animals,
pubmed-meshheading:9582321-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9582321-Cyclooxygenase 2,
pubmed-meshheading:9582321-Dinoprostone,
pubmed-meshheading:9582321-Enzyme Activation,
pubmed-meshheading:9582321-Enzyme Induction,
pubmed-meshheading:9582321-Isoenzymes,
pubmed-meshheading:9582321-MAP Kinase Kinase 4,
pubmed-meshheading:9582321-MAP Kinase Kinase Kinase 1,
pubmed-meshheading:9582321-Mice,
pubmed-meshheading:9582321-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:9582321-Mitogen-Activated Protein Kinases,
pubmed-meshheading:9582321-Phosphorylation,
pubmed-meshheading:9582321-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:9582321-Protein Kinases,
pubmed-meshheading:9582321-Protein-Serine-Threonine Kinases,
pubmed-meshheading:9582321-Protein-Tyrosine Kinases,
pubmed-meshheading:9582321-p38 Mitogen-Activated Protein Kinases
|
|
pubmed:year |
1998
|
|
pubmed:articleTitle |
Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway.
|
|
pubmed:affiliation |
Department of Molecular Biology and Pharmacology and Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|
