Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278) Acosta, Yenny Y Zafra, Maria Paz Ojeda, Gloria Seren Bernardone, Ilaria Dianzani, Umberto Portolés, Pilar Rojo, Jose M PI3-Kinase   Inducible costimulator   ICOS   T lymphocyte Yenny Y. Acosta y Maria Paz Zafra son coautoras de esta publicación científica To better understand T lymphocyte costimulation by inducible costimulator (ICOS; H4; CD278), we analyzed proteins binding to ICOS peptides phosphorylated at the Y(191)MFM motif. Phosphorylated ICOS binds class IA phosphatidyl inositol 3-kinase (PI3-K) p85α, p50-55α and p85β regulatory subunits and p110α, p110δ and p110β catalytic subunits. Intriguingly, T cells expressed high levels of both p110α or p110δ catalytic subunits, yet ICOS peptides, cell surface ICOS or PI3-kinase class IA regulatory subunits preferentially coprecipitated p110α catalytic subunits. Silencing p110α or p110δ partially inhibited Akt/PKB activation induced by anti-CD3 plus anti-ICOS antibodies. However, silencing p110α enhanced and silencing p110δ inhibited Erk activation. Both p110α- and p110δ-specific inhibitors blocked cytokine secretion induced by TCR/CD3 activation with or without ICOS costimulus, but only p110α inhibitors blocked ICOS-induced cell elongation. Thus, p110α and p110δ are essential to optimal T cell activation, but their abundance and activity differentially tune up distinct ICOS signaling pathways. 2025-01-27T08:57:20Z 2025-01-27T08:57:20Z 2011 journal article Acosta YY, Zafra MP, Ojeda G, Bernardone IS, Dianzani U, Portolés P, Rojo JM. Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278). Cell Mol Life Sci. 2011 Sep;68(18):3065-79 PMID: 21188463 https://hdl.handle.net/10481/100419 doi: 10.1007/s00018-010-0606-1. eng open access Springer