SH3 domain-dependent association of huntingtin with epidermal growth factor receptor signaling complexes.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, GRB2 Adaptor Protein, GTPase-Activating Proteins, Humans, Huntington Disease, Macromolecular Substances, Nerve Tissue Proteins, Nuclear Proteins, Proteins, Receptor Protein-Tyrosine Kinases, Receptor, Epidermal Growth Factor, Signal Transduction, Tumor Cells, Cultured, ras GTPase-Activating Proteins, src Homology Domains
Adaptor Proteins, Signal Transducing, GRB2 Adaptor Protein, GTPase-Activating Proteins, Humans, Huntington Disease, Macromolecular Substances, Nerve Tissue Proteins, Nuclear Proteins, Proteins, Receptor Protein-Tyrosine Kinases, Receptor, Epidermal Growth Factor, Signal Transduction, Tumor Cells, Cultured, ras GTPase-Activating Proteins, src Homology Domains
J. Biol. Chem.
Date: Mar. 28, 1997
PubMed ID: 9079622
View in: Pubmed Google Scholar
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