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Access to the article is free, however registration and sign-in are required. A ligand binding to its transmembrane receptor can activate several different signaling pathways that indirectly switch on the transcription of target genes in the nucleus. As Heldin and Ericsson explain in their Perspective, new findings reveal that some receptors such as ErbB-4 can also take a more direct approach to activating gene transcription (Ni et al.). Once bound to ligand, ErbB-4 is proteolytically cleaved twice. First the ectodomain is released, then intramembrane cleavage releases a cytoplasmic fragment, which moves to the nucleus where it may affect gene expression.
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