Phospho-Erk1/2 Pathway Sampler Kit

Mitogen-activated protein kinases (MAPKs) are a widely conserved family of serine/threonine protein kinases involved in many cellular programs, such as cell proliferation, differentiation, motility, and death. The p44/42 MAPK (Erk1/2) signaling pathway can be activated in response to a diverse range of extracellular stimuli, including mitogens, growth factors, and cytokines (1-3), and research investigators consider it an important target in the diagnosis and treatment of cancer (4). Upon stimulation, a sequential three-part protein kinase cascade is initiated, consisting of a MAP kinase kinase kinase (MAPKKK or MAP3K), a MAP kinase kinase (MAPKK or MAP2K), and a MAP kinase (MAPK). Multiple p44/42 MAP3Ks have been identified, including members of the Raf family, as well as Mos and Tpl2/COT. MEK1 and MEK2 are the primary MAPKKs in this pathway (5,6). MEK1 and MEK2 activate p44 and p42 through phosphorylation of activation loop residues Thr202/Tyr204 and Thr185/Tyr187, respectively. Several downstream targets of p44/42 have been identified, including p90RSK (7) and the transcription factor Elk-1 (8,9). p44/42 are negatively regulated by a family of dual-specificity (Thr/Tyr) MAPK phosphatases, known as DUSPs or MKPs (10), along with MEK inhibitors, such as U0126 and PD98059. 1.Roux, P.P. and Blenis, J. (2004) Microbiol Mol Biol Rev 68, 320-44. 2.Baccarini, M. (2005) FEBS Lett 579, 3271-7. 3.Meloche, S. and Pouysségur, J. (2007) Oncogene 26, 3227-39. 4.Roberts, P.J. and Der, C.J. (2007) Oncogene 26, 3291-310. 5.Rubinfeld, H. and Seger, R. (2005) Mol Biotechnol 31, 151-74. 6.Murphy, L.O. and Blenis, J. (2006) Trends Biochem Sci 31, 268-75. 7.Dalby, K.N. et al. (1998) J Biol Chem 273, 1496-505. 8.Marais, R. et al. (1993) Cell 73, 381-93. 9.Kortenjann, M. et al. (1994) Mol Cell Biol 14, 4815-24. 10.Owens, D.M. and Keyse, S.M. (2007) Oncogene 26, 3203-13.