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Engineering NGF receptors to bind Grb2 directly uncovers differences in signaling ability between Grb2‐ and ShcA‐binding sites
Author(s) -
Oku Shinichiro,
van der Meulen Talitha,
Copp Jeremy,
Glenn Gary,
van der Geer Peter
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.08.021
Subject(s) - grb2 , receptor tyrosine kinase , signal transduction , mapk/erk pathway , binding site , microbiology and biotechnology , sh2 domain , receptor , tyrosine kinase , chemistry , biology , biochemistry
Grb2 and ShcA are two phosphotyrosine‐binding proteins that link receptor protein‐tyrosine kinases to activation of the Ras‐Erk pathway. While some receptors bind Grb2 directly, others bind ShcA, which provides a binding site for Grb2. In order to compare signal transduction through a Grb2‐binding site with signal transduction through a ShcA‐binding site, we replaced the ShcA‐binding site in the NGF receptor with a Grb2‐binding site. Our results show that the Grb2‐ and ShcA‐binding sites have similar abilities to activate the Ras‐Erk and PI 3‐kinase‐Akt pathways. In contrast, they displayed dramatic differences in their ability to activate DNA synthesis.