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PMID: 10468633 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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 ·Vol. 96 ·No. 18 ·1999-08-31 ·Pages 10472-6

Verdi JM, Bashirullah A, Goldhawk DE, Kubu CJ, Jamali M, Meakin SO, Lipshitz HD

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.

MeSH Terms
Alternative Splicing Amino Acid Sequence Animals Animals, Genetically Modified Cell Differentiation Cell Division Cell Line Drosophila/genetics Drosophila Proteins Humans Juvenile Hormones/chemistry,genetics,physiology Molecular Sequence Data Multigene Family Neurons/cytology Protein Isoforms/chemistry,genetics,physiology RNA, Messenger/genetics Transcription, Genetic Transfection Wings, Animal/anatomy & histology
Chemicals
Drosophila Proteins Juvenile Hormones Protein Isoforms RNA, Messenger numb protein, Drosophila
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Verdi J M
Robarts Research Institute, London, ON N6A 5K8, Canada.
Bashirullah A
Goldhawk D E
Kubu C J
Jamali M
Meakin S O
Lipshitz H D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.18.10472
Published
1999-08-31
Pages
10472-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC17913
Subset
IM
Databases
GENBANK
AF171938, AF171939, AF171940, AF171941
External Links
PubMed source DOI: 10.1073/pnas.96.18.10472 PMC Full Text View journal details
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