Verdi, J.M., Bashirullah, A., Goldhawk, D.E., Kubu, C.J., Jamali, M., Meakin, S.O., Lipshitz, H.D. (1999). Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage.  Proc. Natl. Acad. Sci. U.S.A. 96(18): 10472--10476.

FBrf0231194

Research paper

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.

PMC17913 (PMC) (EuropePMC)