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Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10472-6.

Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage.

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  • 1Robarts Research Institute, London, ON N6A 5K8, Canada.

Abstract

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
Free PMC Article

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