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Published August 31, 1999 | Published
Journal Article Open

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


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.

Additional Information

© 1999 National Academy of Sciences. Edited by Corey S. Goodman, University of California, Berkeley, CA, and approved June 30, 1999 (received for review April 22, 1999). This paper was submitted directly (Track II) to the Proceedings office. Abbreviations: PTB, phosphotyrosine-binding domain; PRR, prolinerich region; MONC-1, immortalized mouse neural crest cell line. Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF171938, AF171939, AF171940 and AF171941). We thank Pushpa Sharma, Aly Cassam, Cuiping Zhao (Robarts Research Institute), Bill Fisher, and Angelo Karaiskakis (Hospital for Sick Children) for technical assistance. This research was funded in part by grants from the Medical Research Council of Canada (grants MT-14144 to J.M.V. and MT-13208 to H.D.L.). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked ''advertisement'' in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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