Liu Y F, Deth R C, Devys D
Center for Neurological Disease, Brigham and Women's Hospital and Department of Neurology, Harvard Medical School, Boston, Massachusetts 02114, USA.
J Biol Chem. 1997 Mar 28;272(13):8121-4. doi: 10.1074/jbc.272.13.8121.
Based on the presence of multiple proline-rich motifs in the huntingtin sequence, we tested its possible association with epidermal growth factor (EGF) receptor signaling complexes through SH3 domain-containing modules. We found that huntingtin is associated with Grb2, RasGAP, and tyrosine-phosphorylated EGF receptor. These associations are regulated by activation of the EGF receptor, suggesting that they may be part of EGF receptor-mediated cellular signaling cascade. In vitro binding studies indicate that SH3 domains of Grb2 or RasGAP are required for their binding to huntingtin. Our results suggest that huntingtin may be a unique adapter protein for EGF receptor-mediated signaling and may be involved in the regulation of Ras-dependent signaling pathways.
