or 
Receptor Family
Notch
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Summary

Although activation of most plasma membrane receptors ultimately leads to transcriptional changes, very few plasma membrane receptors can serve as both receptors and transcription factors. Notch receptors, the best characterized of this family, transduce signals primarily by nuclear translocation of a cleaved intracellular fragment. The ligands for the Notch family of receptors are Delta, Jagged, and Serrate, a group of membrane-anchored proteins. The Notch receptor is a heterodimer formed from its precursor following cleavage by secretases α and β (94). After ligand binding, the receptor is further cleaved within its transmembrane domain by presenilin-1-associated secretase (95), thereby releasing the intracellular region for nuclear translocation (Fig. 5). This region then binds to transcriptional factors, which together form a complex to regulate gene activity (96). In fly, Notch controls the dorsal-ventral boundary in the developing wing and four mammalian paralogs are known (97). Fringe, a glycosyltransferase, adds O-linked fucose (98) to EGF modules of Notch receptors to regulate their ligand binding.
Relevant reviews and publications:
94. C. M. Blaumueller, H. Qi, P. Zagouras, S. Artavanis-Tsakonas, Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell 90, 281-291 (1997). 95. Y. Taniguchi, H. Karlstrom, J. Lundkvist, T. Mizutani, A. Otaka, M. Vestling, A. Bernstein, D. Donoviel, U. Lendahl, T. Honjo, Notch receptor cleavage depends on but is not directly executed by presenilins. Proc Natl Acad Sci U S A 99, 4014-4019 (2002). 96. C. Kiecker, C. Niehrs, The role of prechordal mesendoderm in neural patterning. Curr Opin Neurobiol 11, 27-33 (2001). 97. T. Mizutani, Y. Taniguchi, T. Aoki, N. Hashimoto, T. Honjo, Conservation of the biochemical mechanisms of signal transduction among mammalian Notch family members. Proc Natl Acad Sci U S A 98, 9026-9031 (2001). 98. S. Goto, M. Taniguchi, M. Muraoka, H. Toyoda, Y. Sado, M. Kawakita, S. Hayashi, UDP-sugar transporter implicated in glycosylation and processing of Notch. Nat Cell Biol 3, 816-822 (2001).
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