title: 8-Bromo-cAMP induces a proliferative response in an IL-3 dependent leukemic cell line and activates Erk 1,2 via a Shc-independent pathway.
abstract: In a number of cell types, elevation of intracellular cAMP concentrations antagonizes growth factor-induced mitogenesis by abrogating the downstream signaling of RasGTP to extracellular-signal-regulated kinases (Erk 1,2). We studied the effect of elevation of cAMP concentrations on the IL-3-induced mitogenic response in the leukemic cell line AML193. We observed that 8-bromo-cAMP (8-Br-cAMP) had no inhibitory effect on the magnitude of this response. On the contrary. 8-Br-cAMP alone induced a proliferative response in these cells. 8-Br-cAMP activated Erk 1,2 in these cells without involvement of Shc phosphorylation. These findings suggest the presence of a novel cAMP-dependent signaling pathway in AML193 cells, which activates Erk 1,2 via a Shc-independent pathway and leads to the generation of a mitogenic response.
authors.affiliation: Department of Medical Biochemistry, University of Leiden, The Netherlands.
authors.forename: R M
authors.initials: RM
authors.lastname: Barge
authors.forename: J H
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: R
authors.initials: R
authors.lastname: Willemze
authors.forename: J A
authors.initials: JA
authors.lastname: Maassen
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007377:Interleukin-3 / Q000494:pharmacology; D007938:Leukemia; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008934:Mitogens / Q000494:pharmacology*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D007377:Interleukin-3; D008934:Mitogens; D015124:8-Bromo Cyclic Adenosine Monophosphate; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases