Proteomics

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


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell

SUBMITTER: Nerea Osinalde  

LAB HEAD: Irina kratchmarova

PROVIDER: PXD003286 | Pride | 2016-04-11

REPOSITORIES: Pride

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Publications

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

Osinalde Nerea N   Sánchez-Quiles Virginia V   Blagoev Blagoy B   Kratchmarova Irina I  

Scientific reports 20160330


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  ...[more]

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