Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278)

Yenny Y. Acosta, Maria Paz Zafra, Gloria Ojeda, Ilaria Seren Bernardone, Umberto Dianzani, Pilar Portolés, Jose M. Rojo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

16 Citas (Scopus)

Resumen

To better understand T lymphocyte costimulation by inducible costimulator (ICOS; H4; CD278), we analyzed proteins binding to ICOS peptides phosphorylated at the Y191MFM 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 p110a 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 p110d are essential to optimal T cell activation, but their abundance and activity differentially tune up distinct ICOS signaling pathways.

Idioma originalInglés estadounidense
Páginas (desde-hasta)3065-3079
Número de páginas15
PublicaciónCellular and Molecular Life Sciences
Volumen68
N.º18
DOI
EstadoPublicada - sep. 2011
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Medicina molecular
  • Biología molecular
  • Farmacología
  • Neurociencia celular y molecular
  • Biología celular

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