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Despite the success of tyrosine kinase-based cancer therapeutics, for most solid tumors the tyrosine kinases that drive disease remain unknown, limiting our ability to identify drug targets and predict response. Here we present the first large-scale survey of tyrosine kinase activity in lung cancer. Using a phosphoproteomic approach, we characterize tyrosine kinase signaling across 41 non-small cell...
The transcription factor CREB mediates diverse responses in the nervous system. It is not known how CREB induces specific patterns of gene expression in response to different extracellular stimuli. We find that Ca2+ influx into neurons induces CREB phosphorylation at Ser133 and two additional sites, Ser142 and Ser143. While CREB Ser133 phosphorylation is induced by many stimuli, phosphorylation at...
We used positional cloning to identify the circadian Clock gene in mice. Clock is a large transcription unit with 24 exons spanning ∼100,000 bp of DNA from which transcript classes of 7.5 and ∼10 kb arise. Clock encodes a novel member of the bHLH–PAS family of transcription factors. In the Clock mutant allele, an A→T nucleotide transversion in a splice donor site causes exon skipping and deletion...
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