Cellular and Molecular Life Sciences

, Volume 68, Issue 18, pp 3065–3079

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
Research Article

DOI: 10.1007/s00018-010-0606-1

Cite this article as:
Acosta, Y.Y., Zafra, M.P., Ojeda, G. et al. Cell. Mol. Life Sci. (2011) 68: 3065. doi:10.1007/s00018-010-0606-1

Abstract

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 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.

Keywords

PI3-KinaseInducible costimulatorICOST lymphocyte

Supplementary material

18_2010_606_MOESM1_ESM.pdf (907 kb)
Supplementary material 1 (PDF 907 kb)

Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Yenny Y. Acosta
    • 1
  • Maria Paz Zafra
    • 1
  • Gloria Ojeda
    • 2
  • Ilaria Seren Bernardone
    • 1
    • 3
  • Umberto Dianzani
    • 3
  • Pilar Portolés
    • 2
  • Jose M. Rojo
    • 1
  1. 1.Departamento de Medicina Celular y Molecular, Centro de Investigaciones Biológicas, CSICMadridSpain
  2. 2.Centro Nacional de Microbiología, Instituto de Salud Carlos III, MajadahondaMadridSpain
  3. 3.Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD)“A. Avogadro” University of Eastern PiedmontNovaraItaly