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1: Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10472-6.Click here to read Click here to read Links

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