Research ResourceMAPK Signaling

Proteomic and Functional Genomic Landscape of Receptor Tyrosine Kinase and Ras to Extracellular Signal–Regulated Kinase Signaling

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Science Signaling  25 Oct 2011:
Vol. 4, Issue 196, pp. rs10
DOI: 10.1126/scisignal.2002029

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Finding the Shared and the Specific Components Regulating MAPK Signals

Even in extensively studied pathways, such as the extracellular signal–regulated kinase (ERK) pathway that is activated by receptor tyrosine kinases, there remain gaps in our knowledge. Friedman et al. combined protein-protein interaction screens with RNAi functional genomic screens in Drosophila cell lines to identify components of the ERK pathway downstream of two receptor tyrosine kinases. Their analysis suggested that these receptors may compete for some common components, in addition to using receptor-specific and cell-specific signal transduction pathways. Knockdown of several newly identified pathway regulators resulted in wing phenotypes in vivo, confirming these as components in the pathway. Detailed understanding of this pathway has clinical relevance because of its importance in both physiological and pathophysiological contexts, such as cell fate decisions and mechanisms of oncogenesis and resistance to chemotherapy.

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