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@ARTICLE{KazemeinJasemi:904331,
author = {Kazemein Jasemi, Neda S. and Herrmann, Christian and
Magdalena Estirado, Eva and Gremer, Lothar and Willbold,
Dieter and Brunsveld, Luc and Dvorsky, Radovan and Ahmadian,
Mohammad R.},
title = {{T}he intramolecular allostery of {GRB}2 governing its
interaction with {SOS}1 is modulated by phosphotyrosine
ligands},
journal = {Biochemical journal},
volume = {478},
number = {14},
issn = {0006-2936},
address = {London},
publisher = {Portland Press},
reportid = {FZJ-2021-05901},
pages = {2793 - 2809},
year = {2021},
note = {Kein Post-print vorhanden},
abstract = {Growth factor receptor-bound protein 2 (GRB2) is a
trivalent adaptor protein and a key element in signal
transduction. It interacts via its flanking nSH3 and cSH3
domains with the proline-rich domain (PRD) of the RAS
activator SOS1 and via its central SH2 domain with
phosphorylated tyrosine residues of receptor tyrosine
kinases (RTKs; e.g. HER2). The elucidation of structural
organization and mechanistic insights into GRB2
interactions, however, remain challenging due to their
inherent flexibility. This study represents an important
advance in our mechanistic understanding of how GRB2 links
RTKs to SOS1. Accordingly, it can be proposed that (1) HER2
pYP-bound SH2 potentiates GRB2 SH3 domain interactions with
SOS1 (an allosteric mechanism); (2) the SH2 domain blocks
cSH3, enabling nSH3 to bind SOS1 first before cSH3 follows
(an avidity-based mechanism); and (3) the allosteric
behavior of cSH3 to other domains appears to be
unidirectional, although there is an allosteric effect
between the SH2 and SH3 domains.},
cin = {IBI-7},
ddc = {540},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34232285},
UT = {WOS:000683548100006},
doi = {10.1042/BCJ20210105},
url = {https://juser.fz-juelich.de/record/904331},
}