Mutant huntingtin replaces Gab1 and interacts with C-terminal SH3 domain of growth factor receptor binding protein 2 (Grb2)

Shounak Baksi; Sreetama Basu; Debashis Mukhopadhyay

doi:10.1016/j.neures.2014.06.009

Mutant huntingtin replaces Gab1 and interacts with C-terminal SH3 domain of growth factor receptor binding protein 2 (Grb2)

Shounak Baksi
, Sreetama Basu
, Debashis Mukhopadhyay

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	77-83
Number of pages	7
Journal	Neuroscience Research
Volume	87
Issue number	C
DOIs	https://doi.org/10.1016/j.neures.2014.06.009
State	Published - 2014
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Grb2
Htt
Interaction
MAPK signaling
SH3 domain

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1016/j.neures.2014.06.009

Cite this

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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.",

keywords = "Grb2, Htt, Interaction, MAPK signaling, SH3 domain",

author = "Shounak Baksi and Sreetama Basu and Debashis Mukhopadhyay",

note = "Publisher Copyright: {\textcopyright} 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society.",

year = "2014",

doi = "10.1016/j.neures.2014.06.009",

language = "English",

volume = "87",

pages = "77--83",

journal = "Neuroscience Research",

issn = "0168-0102",

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T1 - Mutant huntingtin replaces Gab1 and interacts with C-terminal SH3 domain of growth factor receptor binding protein 2 (Grb2)

AU - Baksi, Shounak

AU - Basu, Sreetama

AU - Mukhopadhyay, Debashis

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Grb2

KW - Htt

KW - Interaction

KW - MAPK signaling

KW - SH3 domain

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DO - 10.1016/j.neures.2014.06.009

M3 - Article

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AN - SCOPUS:84927567895

SN - 0168-0102

VL - 87

SP - 77

EP - 83

JO - Neuroscience Research

JF - Neuroscience Research

IS - C

ER -

Mutant huntingtin replaces Gab1 and interacts with C-terminal SH3 domain of growth factor receptor binding protein 2 (Grb2)

Abstract

Bibliographical note

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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