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.
Verdi
J M
JM
Robarts Research Institute, London, ON N6A 5K8, Canada.
Bashirullah
A
A
Goldhawk
D E
DE
Kubu
C J
CJ
Jamali
M
M
Meakin
S O
SO
Lipshitz
H D
HD
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D006801:Humans; D007605:Juvenile Hormones / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009474:Neurons / Q000166:cytology*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D014921:Wings, Animal / Q000033:anatomy & histology
D029721:Drosophila Proteins; D007605:Juvenile Hormones; D020033:Protein Isoforms; D012333:RNA, Messenger; C060606:numb protein, Drosophila