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Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage.
Robarts Research Institute, London, ON N6A 5K8, Canada.
Neuronal cell fate decisions are directed in Drosophila by NUMB, a signaling adapter protein with two protein-protein interaction domains: a phosphotyrosine-binding domain and a proline-rich region (PRR) that functions as an SH3-binding domain. Here we show that there are at least four human NUMB isoforms and that these serve two distinct developmental functions in the neuronal lineage: differentiation (but not proliferation) is promoted by human NUMB protein isoforms with a type I (short) PRR. In contrast, proliferation (but not differentiation) is directed by isoforms that have a type II (long) PRR. The two types of PRR may promote distinct intracellular signaling pathways downstream of the NOTCH receptor during mammalian neurogenesis.
PMID: 10468633 [PubMed - indexed for MEDLINE]
PMCID: PMC17913
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Cited by 7 PubMed Central articles
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Gene expression signature of cerebellar hypoplasia in a mouse model of Down syndrome during postnatal development.
Laffaire J, Rivals I, Dauphinot L, Pasteau F, Wehrle R, Larrat B, Vitalis T, Moldrich RX, Rossier J, Sinkus R, et al.
BMC Genomics. 2009 Mar 30; 10:138. Epub 2009 Mar 30.
[BMC Genomics. 2009]
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Numb proteins specify asymmetric cell fates via an endocytosis- and proteasome-independent pathway.
Tang H, Rompani SB, Atkins JB, Zhou Y, Osterwalder T, Zhong W.
Mol Cell Biol. 2005 Apr; 25(8):2899-909.
[Mol Cell Biol. 2005]
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The gamma-secretase-generated intracellular domain of beta-amyloid precursor protein binds Numb and inhibits Notch signaling.
Roncarati R, Sestan N, Scheinfeld MH, Berechid BE, Lopez PA, Meucci O, McGlade JC, Rakic P, D'Adamio L.
Proc Natl Acad Sci U S A. 2002 May 14; 99(10):7102-7.
[Proc Natl Acad Sci U S A. 2002]
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