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

13 Citations (Scopus)

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

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Actins
Cytoskeleton
T-Lymphocytes
Phosphatidylinositol 4,5-Diphosphate
Second Messenger Systems
Phosphatidylinositols
Proline
Polymerization
Phosphotransferases
Cell Membrane
Lipids
1-phosphatidylinositol-4-phosphate 5-kinase
Proteins

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Muscolini, M., Camperio, C., Porciello, N., Caristi, S., Capuano, C., Viola, A., ... 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

Phosphatidylinositol 4-phosphate 5-kinase a and vav1 mutual cooperation in CD28-mediated actin remodeling and signaling functions. / Muscolini, Michela; Camperio, Cristina; Porciello, Nicla; Caristi, Silvana; Capuano, Cristina; Viola, Antonella; Galandrini, Ricciarda; Tuosto, Loretta.

In: Journal of Immunology, Vol. 194, No. 3, 01.02.2015, p. 1323-1333.

Research output: Contribution to journalArticle

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, vol. 194, no. 3, pp. 1323-1333. https://doi.org/10.4049/jimmunol.1401643
Muscolini, Michela ; Camperio, Cristina ; Porciello, Nicla ; Caristi, Silvana ; Capuano, Cristina ; Viola, Antonella ; Galandrini, Ricciarda ; Tuosto, Loretta. / Phosphatidylinositol 4-phosphate 5-kinase a and vav1 mutual cooperation in CD28-mediated actin remodeling and signaling functions. In: Journal of Immunology. 2015 ; Vol. 194, No. 3. pp. 1323-1333.
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