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On page 1133, Bao et al. demonstrate that a neuronal growth factor signals to neighboring cells while also communicating back to the nucleus of its own cell. This two-way signaling is necessary to maintain neuronal survival.1 z4 n9 |, q% c. i0 ]$ d% v0 o
/ y! c# V2 b1 r; b4 r# b/ t9 PIn the forward direction, either a soluble or membrane-bound form of the Nrg-1 growth factor activates erbB receptor tyrosine kinases on a variety of adjacent cells. The Nrg-1/erbB partnership is well known to control responses in the erbB-expressing cells, such as epithelial cell motility and proliferation, through MAP kinase pathways. Now, the target cells are shown to talk back to neurons that express membrane-bound Nrg-1 via the same erbB–Nrg-1 complex.Bao et al. show that treatment with soluble erbB protects Nrg-1–expressing neurons from cell death in vitro. The protective activity appears to stem from Nrg-1's ability to regulate transcription of apoptotic genes, including BAK and RIP, whose expression levels were repressed by treatment with erbB. Membrane-bound Nrg-1 was cleaved by a -secretase–like activity in response to erbB treatment, thus releasing the Nrg-1 intracellular domain, which moved to the nucleus. Although Nrg-1 has not been shown to bind to DNA, the authors demonstrate that it does has transactivating activity on a reporter construct, and preliminary evidence indicates it may interact with zinc finger–containing transcription factors.(The intracellular domain of Nrg-1 (red) ) |
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发表于 2009-3-6 00:54
发表于 2015-6-27 09:18
