Phosphatidylinositol 4-phosphate 5-kinase a and vav1 mutual cooperation in CD28-mediated actin remodeling and signaling functions

Michela Muscolini, Cristina Camperio, Nicla Porciello, Silvana Caristi, Cristina Capuano, Antonella Viola, Ricciarda Galandrini, Loretta Tuosto

Research output: Contribution to journalArticle

Abstract

Phosphatidylinositol 4,5-biphosphate (PIP2) is a cell membrane phosphoinositide crucial for cell signaling and activation. Indeed, PIP2 is a pivotal source for second messenger generation and controlling the activity of several proteins regulating cytoskeleton reorganization. Despite its critical role in T cell activation, the molecular mechanisms regulating PIP2 turnover remain largely unknown. In human primary CD4+ T lymphocytes, we have recently demonstrated that CD28 costimulatory receptor is crucial for regulating PIP2 turnover by allowing the recruitment and activation of the lipid kinase phosphatidylinositol 4-phosphate 5-kinase (PIP5Kα). We also identified PIP5Ka as a key modulator of CD28 costimulatory signals leading to the efficient T cell activation. In this study, we extend these data by demonstrating that PIP5Ka recruitment and activation is essential for CD28-mediated cytoskeleton rearrangement necessary for organizing a complete signaling compartment leading to downstream signaling functions. We also identified Vav1 as the linker molecule that couples the C-terminal proline-rich motif of CD28 to the recruitment and activation of PIP5Ka, which in turn cooperates with Vav1 in regulating actin polymerization and CD28 signaling functions.

Original languageEnglish
Pages (from-to)1323-1333
Number of pages11
JournalJournal of Immunology
Volume194
Issue number3
DOIs
Publication statusPublished - Feb 1 2015

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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    Muscolini, M., Camperio, C., Porciello, N., Caristi, S., Capuano, C., Viola, A., Galandrini, R., & Tuosto, L. (2015). Phosphatidylinositol 4-phosphate 5-kinase a and vav1 mutual cooperation in CD28-mediated actin remodeling and signaling functions. Journal of Immunology, 194(3), 1323-1333. https://doi.org/10.4049/jimmunol.1401643