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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alternative Splicing
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Cell Differentiation
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Cell Division
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Cell Line
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Drosophila / genetics*
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Drosophila Proteins
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Humans
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Juvenile Hormones / chemistry
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Juvenile Hormones / genetics*
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Juvenile Hormones / physiology*
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Molecular Sequence Data
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Multigene Family
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Neurons / cytology*
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Protein Isoforms / chemistry
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Protein Isoforms / genetics
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Protein Isoforms / physiology
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RNA, Messenger / genetics
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Transcription, Genetic
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Transfection
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Wings, Animal / anatomy & histology
Substances
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Drosophila Proteins
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Juvenile Hormones
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Protein Isoforms
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RNA, Messenger
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numb protein, Drosophila
Associated data
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GENBANK/AF171938
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GENBANK/AF171939
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GENBANK/AF171940
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GENBANK/AF171941