Functional proteomics provides a powerful method for monitoring global molecular responses following activation of signal transduction pathways, reporting altered protein posttranslational modification and expression. Here we combine functional proteomics with selective activation and inhibition of MKK1/2, in order to identify cellular targets regulated by the MKK/ERK cascade. Twenty-five targets of this signaling pathway were identified, of which only five were previously characterized as MKK/ERK effectors. The remaining targets suggest novel roles for this signaling cascade in cellular processes of nuclear transport, nucleotide excision repair, nucleosome assembly, membrane trafficking, and cytoskeletal regulation. This study represents an application of functional proteomics toward identifying regulated targets of a discrete signal transduction pathway and demonstrates the utility of this discovery-based strategy in elucidating novel MAP kinase pathway effectors.
Increased marine 14C reservoir ages from the surface water of the North Atlantic are documented for the Younger Dryas period. We use terrestrial and marine AMS 14C dates from the time of deposition of the Icelandic Vedde Ash to examine the marine 14C reservoir age. This changed from its modem North Atlantic value of ca. 400 yr to ca. 700 yr during the Younger Dryas climatic event. The increased marine reservoir age has implications for both comparing climatic time series dated by 14C and understanding palaeoceanographic changes that generated the increase.
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