Publication Date:
1993-11-12
Description:
Mitogen-activated protein (MAP) kinases p42mapk and p44mapk are activated in cells stimulated with epidermal growth factor (EGF) and other agents. A principal pathway for MAP kinase (MAPK) activation by EGF consists of sequential activations of the guanine nucleotide exchange factor Sos, the guanosine triphosphate binding protein Ras, and the protein kinases Raf-1, MAPK kinase (MKK), and MAPK. Because adenosine 3',5'-monophosphate (cAMP) does not activate MAPK and has some opposing physiologic effects, the effect of increasing intracellular concentrations of cAMP with forskolin and 3-isobutyl-1-methylxanthine on the EGF-stimulated MAPK pathway was studied. Increased concentrations of cAMP blocked activation of Raf-1, MKK, and MAPK in Rat1hER fibroblasts, accompanied by a threefold increase in Raf-1 phosphorylation on serine 43 in the regulatory domain. Phosphorylation of Raf-1 in vitro and in vivo reduces the apparent affinity with which it binds to Ras and may contribute to the blockade by cAMP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, J -- Dent, P -- Jelinek, T -- Wolfman, A -- Weber, M J -- Sturgill, T W -- CA39076/CA/NCI NIH HHS/ -- DK41077/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1993 Nov 12;262(5136):1065-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, University of Virginia, Health Sciences Center, Charlottesville 22908.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7694366" target="_blank"〉PubMed〈/a〉
Keywords:
1-Methyl-3-isobutylxanthine/pharmacology
;
3T3 Cells
;
Amino Acid Sequence
;
Animals
;
Cell Line
;
Colforsin/pharmacology
;
Cyclic AMP/*metabolism
;
Cyclic AMP-Dependent Protein Kinases/metabolism
;
Enzyme Activation/drug effects
;
Epidermal Growth Factor/*pharmacology
;
Mice
;
Mitogen-Activated Protein Kinase 1
;
Mitogen-Activated Protein Kinase Kinases
;
Molecular Sequence Data
;
Phosphorylation
;
Protein Kinases/metabolism
;
Protein-Serine-Threonine Kinases/*metabolism
;
Protein-Tyrosine Kinases/*metabolism
;
Proto-Oncogene Proteins/metabolism
;
Proto-Oncogene Proteins c-raf
;
Proto-Oncogene Proteins p21(ras)/*metabolism
;
Rats
;
*Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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