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Because adenosine 3\u2032,5\u2032-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.\n          <\/jats:p>","DOI":"10.1126\/science.7694366","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T23:05:09Z","timestamp":1160089509000},"page":"1065-1069","source":"Crossref","is-referenced-by-count":728,"title":["Inhibition of the EGF-Activated MAP Kinase Signaling Pathway by Adenosine 3\u2032,5\u2032-Monophosphate"],"prefix":"10.1126","volume":"262","author":[{"given":"Jie","family":"Wu","sequence":"first","affiliation":[{"name":"Departments of Internal Medicine and Pharmacology, University of Virginia Health Sciences Center, Charlottesville, VA 22908."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Dent","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine and Pharmacology, University of Virginia Health Sciences Center, 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