Publication Date:
1993-11-12
Description:
Activation of the Raf and extracellular signal-regulated kinases (ERKs) (or mitogen-activated protein kinases) are key events in mitogenic signalling, but little is known about interactions with other signaling pathways. Agents that raise levels of intracellular cyclic adenosine 3',5'-monophosphate (cAMP) blocked DNA synthesis and signal transduction in Rat1 cells exposed to epidermal growth factor (EGF) or lysophosphatidic acid. In the case of EGF, receptor tyrosine kinase activity and association with the signaling molecules Grb2 and Shc were unaffected by cAMP. Likewise, EGF-dependent accumulation of the guanosine 5'-triphosphate-bound form of Ras was unaffected. In contrast, activation of Raf-1 and ERK kinases was inhibited. Thus, cAMP appears to inhibit signal transmission from Ras by preventing Ras-dependent activation of Raf-1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cook, S J -- McCormick, F -- UO1 CA51992-03/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Nov 12;262(5136):1069-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Onyx Pharmaceuticals, Richmond, CA 94806.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7694367" target="_blank"〉PubMed〈/a〉
Keywords:
1-Methyl-3-isobutylxanthine/pharmacology
;
Animals
;
Bucladesine/pharmacology
;
Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
;
Cell Line
;
Cholera Toxin/pharmacology
;
Cyclic AMP/*pharmacology
;
Cyclic AMP-Dependent Protein Kinases/metabolism
;
Enzyme Activation
;
Epidermal Growth Factor/pharmacology
;
Interphase
;
Lysophospholipids/pharmacology
;
Mitogen-Activated Protein Kinase 1
;
Mitogen-Activated Protein Kinase 3
;
*Mitogen-Activated Protein Kinases
;
Phosphorylation
;
Protein-Tyrosine Kinases/*metabolism
;
Proto-Oncogene Proteins/*metabolism
;
Proto-Oncogene Proteins c-raf
;
Proto-Oncogene Proteins p21(ras)/*metabolism
;
Rats
;
Receptor, Epidermal Growth Factor/metabolism
;
*Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
