title: Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance.
abstract: In the present paper, we describe multiple levels of cross-talk between the PI3K (phosphoinositide 3-kinase)/Akt and Ras/MAPK (mitogen-activated protein kinase) signalling pathways. Experimental data and computer simulations demonstrate that cross-talk is context-dependent and that both pathways can activate or inhibit each other. Positive influence of the PI3K pathway on the MAPK pathway is most effective at sufficiently low doses of growth factors, whereas negative influence of the MAPK pathway on the PI3K pathway is mostly pronounced at high doses of growth factors. Pathway cross-talk endows a cell with emerging capabilities for processing and decoding signals from multiple receptors activated by different combinations of extracellular cues.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Edita
authors.initials: E
authors.lastname: Aksamitiene
authors.forename: Anatoly
authors.initials: A
authors.lastname: Kiyatkin
authors.forename: Boris N
authors.initials: BN
authors.lastname: Kholodenko
mesh_terms: D002470:Cell Survival; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D060066:Protein Interaction Maps; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020239:Receptor Cross-Talk; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins