Phosphatidylinositol 4,5-biphosphate (PIP2) is critical for T lymphocyte activation serving as a substrate for the generation of second messengers and the remodeling of actin cytoskeleton necessary for the clustering of lipid rafts, TCR, and costimulatory receptors toward the T:APC interface. Spatiotemporal analysis of PIP2 synthesis in T lymphocytes suggested that distinct isoforms of the main PIP2-generating enzyme, phosphatidylinositol 4-phosphate 5-kinase (PIP5K), play a differential role on the basis of their distinct localization. In this study, we analyze the contribution of PIP5Kb to T cell activation and show that CD28 induces the recruitment of PIP5Kb to the immunological synapse, where it regulates filamin A and lipid raft accumulation, as well as T cell activation, in a nonredundant manner. Finally, we found that Vav1 and the C-terminal 83 aa of PIP5Kb are pivotal for the PIP5Kb regulatory functions in response to CD28 stimulation.

Phosphatidylinositol 4-phosphate 5-kinase β controls recruitment of lipid rafts into the immunological synapse / Kallikourdis, Marinos; Trovato, Anna Elisa; Roselli, Giuliana; Muscolini, Michela; Porciello, Nicla; Tuosto, Loretta; Viola, Antonella. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - ELETTRONICO. - 196:4(2016), pp. 1955-1963. [10.4049/jimmunol.1501788]

Phosphatidylinositol 4-phosphate 5-kinase β controls recruitment of lipid rafts into the immunological synapse

MUSCOLINI, MICHELA
Investigation
;
PORCIELLO, NICLA
Investigation
;
TUOSTO, Loretta
Penultimo
Writing – Original Draft Preparation
;
2016

Abstract

Phosphatidylinositol 4,5-biphosphate (PIP2) is critical for T lymphocyte activation serving as a substrate for the generation of second messengers and the remodeling of actin cytoskeleton necessary for the clustering of lipid rafts, TCR, and costimulatory receptors toward the T:APC interface. Spatiotemporal analysis of PIP2 synthesis in T lymphocytes suggested that distinct isoforms of the main PIP2-generating enzyme, phosphatidylinositol 4-phosphate 5-kinase (PIP5K), play a differential role on the basis of their distinct localization. In this study, we analyze the contribution of PIP5Kb to T cell activation and show that CD28 induces the recruitment of PIP5Kb to the immunological synapse, where it regulates filamin A and lipid raft accumulation, as well as T cell activation, in a nonredundant manner. Finally, we found that Vav1 and the C-terminal 83 aa of PIP5Kb are pivotal for the PIP5Kb regulatory functions in response to CD28 stimulation.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/954247
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