Characterization of receptor-associated protein complex assembly in interleukin (IL)-2- and IL-15-activated T-cell lines

Nerea Osinalde, Virginia Sánchez-Quiles, Vyacheslav Akimov, Kerman Aloria, Jesus M Arizmendi, Blagoy Blagoev, Irina Kratchmarova

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

It remains a paradox that IL-2 and IL-15 can differentially modulate the immune response using the same signaling receptors. We have previously dissected the phosphotyrosine-driven signaling cascades triggered by both cytokines in Kit225 T-cells, unveiling subtle differences that may contribute to their functional dichotomy. In this study, we aimed to decipher the receptor complex assembly in IL-2- and IL-15-activated T-lymphocytes that is highly orchestrated by site-specific phosphorylation events. Comparing the cytokine-induced interactome of the interleukin receptor beta and gamma subunits shared by the two cytokines, we defined the components of the early IL-2 and IL-15 receptor-associated complex discovering novel constituents. Additionally, phosphopeptide-directed analysis allowed us to detect several cytokine-dependent and -independent phosphorylation events within the activated receptor complex including novel phosphorylated sites located in the cytoplasmic region of IL-2 receptor β subunit (IL-2Rβ). We proved that the distinct phosphorylations induced by the cytokines serve for recruiting different types of effectors to the initial receptor/ligand complex. Overall, our study sheds new light into the initial molecular events triggered by IL-2 and IL-15 and constitutes a further step toward a better understanding of the early signaling aspects of the two closely related cytokines in T-lymphocytes.

Original languageEnglish
JournalJournal of Proteome Research
Volume16
Issue number1
Pages (from-to)106-121
ISSN1535-3893
DOIs
Publication statusPublished - 6. Jan 2017

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