title: Mutant huntingtin replaces Gab1 and interacts with C-terminal SH3 domain of growth factor receptor binding protein 2 (Grb2).
abstract: Huntington's disease (HD) is caused due to expansion of CAG repeats in the gene huntingtin (Htt). Adaptor protein Grb2, involved in Ras-MAP kinase pathway, is a known interactor of Htt. Mutant Htt-Grb2 interaction reduces Ras-MAPK signaling in HD models. In normal cells Grb2 forms Grb2-Sos1-Gab1 complex through its N-SH3 and C-SH3 domains respectively, essential for sustained activation of Ras. We found that C-SH3 of Grb2 mediates the interaction with mutant Htt and this interaction being stronger could replace Gab1, with mutant Htt becoming the preferred partner. This would have immense effect on downstream signaling events.
authors.affiliation: Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata 700064, India.
authors.forename: Shounak
authors.initials: S
authors.lastname: Baksi
authors.affiliation: Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata 700064, India.
authors.forename: Sreetama
authors.initials: S
authors.lastname: Basu
authors.affiliation: Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata 700064, India. Electronic address: debashis.mukhopadhyay@saha.ac.in.
authors.forename: Debashis
authors.initials: D
authors.lastname: Mukhopadhyay
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D051380:GRB2 Adaptor Protein / Q000378:metabolism*; D006801:Humans; D000071058:Huntingtin Protein; D020935:MAP Kinase Signaling System; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C098587:GAB1 protein, human; D051380:GRB2 Adaptor Protein; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins
keywords: Grb2; Htt; Interaction; MAPK signaling; SH3 domain