Activation of the MAP kinase signaling pathway elicits variable responses, depending on the cellular context. Identifying changes in protein expression can lead to insight into how MAP kinase signaling can regulate a certain biological response. Lewis et al. have applied a combination of functional proteomics and mass spectrometry to identify 20 new downstream targets of the MAP kinase signaling pathway, according to changes in their abundance and/or modifications, in a human erythroleukemia cell line treated with a phorbol ester. The strategy involved activation and suppression of the pathway by expressing active kinase mutants or applying cell-permeable inhibitors. The new targets indicate that the regulatory roles of the MAP kinase pathway may be even broader than what is currently realized, including nuclear transport, membrane trafficking, and nucleotide excision repair.
Lewis, T.S., Hunt, J.B., Aveline, L.D., Jonscher, K.R., Louie, D.F., Yeh, J.M., Nahreini, T.S., Resing, K.A., and Ahn, N.G. (2000) Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry. Mol. Cell 6: 1343-1354. [Online Journal]