SH3 DOMAIN-DEPENDENT ASSOCIATION OF HUNTINGTON WITH EPIDERMAL GROWTH-FACTOR RECEPTOR SIGNALING COMPLEXES

Based on the presence of multiple proline-rich moths in the huntingtin sequence, we tested its possible association with epidermal growth fa ctor (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 regulate d 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 t heir 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 Bus-dependent signaling pathways.