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

Verdi, Joseph M. and Bashirullah, Arash and Goldhawk, Donna E. and Kubu, Chris J. and Jamali, Mina and Meakin, Susan O. and Lipshitz, Howard D. (1999) Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage. Proceedings of the National Academy of Sciences of the United States of America, 96 (18). pp. 10472-10476. ISSN 0027-8424. PMCID PMC17913. doi:10.1073/pnas.96.18.10472.

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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.

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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.
Funding AgencyGrant Number
Medical Research Council of CanadaMT-14144
Medical Research Council of CanadaMT-13208
Issue or Number:18
PubMed Central ID:PMC17913
Record Number:CaltechAUTHORS:20141125-132714294
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Official Citation:Joseph M. Verdi, Arash Bashirullah, Donna E. Goldhawk, Chris J. Kubu, Mina Jamali, Susan O. Meakin, and Howard D. Lipshitz Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage PNAS 1999 96 (18) 10472-10476; doi:10.1073/pnas.96.18.10472
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52150
Deposited By: Tony Diaz
Deposited On:26 Nov 2014 20:01
Last Modified:10 Nov 2021 19:21

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