MassIVE MSV000080707

Partial Public PXD003286

Changes in Gab2 phosphorylation and interaction partners in response to interleukin (IL)-2 stimulation in T-lymphocytes

Description

Interleukin-2 (IL-2) stimulation results in T-cell growth as a consequence of activation of highly sophisticated and fine-tuned signaling pathways. Despite lacking intrinsic enzymatic activity, scaffold proteins such as Gab2, play a pivotal role in IL-2-triggered signal transduction integrating, diversifying and amplifying the signal by serving as a platform for the assembly of effectors proteins. Traditionally, Gab2-mediated protein recruitment was believed to solely depend on cytokine-induced phosphotyrosine moieties. At present, increasing body of literature indicates that phosphorylation on serine/threonine residues are emerging also as key mediators of Gab2-dependent signal regulation. Despite its relevance, IL-2-triggered regulation on Gab2 phosphorylation is yet poorly understood. Combining antibody- and TiO2-based enrichment of Gab2 with SILAC quantitative mass spectrometry we disclose the prominent regulation on serine/threonine phosphorylated residues of Gab2 by IL-2 showing that at least 18 serines and 1 threonine, including previously non-reported ones, become phosphorylated in response to the cytokine. Additionally, we deciphered the interactome of the scaffold protein in resting and cytokine-treated T-lymphocytes and besides well-known Gab2 interactors we uncover three novel cytokine-inducible Gab2-binding proteins. Thus, our data provide novel insights and a wealth of candidates for future studies that will shed light into the role of Gab2 in IL-2-initiated signal transduction. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: IL-2 ; GAB2 ; phosphorylation ; interactome ; scaffold protein ; T-lymphocytes

Contact

Principal Investigators:
(in alphabetical order)
Irina kratchmarova, Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark., N/A
Submitting User: ccms

Publications

Osinalde N, Sánchez-Quiles V, Blagoev B, Kratchmarova I.
Changes in Gab2 phosphorylation and interaction partners in response to interleukin (IL)-2 stimulation in T-lymphocytes.
Sci Rep. Epub 2016 Mar 30.

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