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.
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.
Barge
R M
RM
Department of Medical Biochemistry, University of Leiden, The Netherlands.
Falkenburg
J H
JH
Willemze
R
R
Maassen
J A
JA
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
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