title: Phosphatidylinositol 4-phosphate 5-kinase α and Vav1 mutual cooperation in CD28-mediated actin remodeling and signaling functions.
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 PIP5Kα 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 PIP5Kα 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 PIP5Kα, which in turn cooperates with Vav1 in regulating actin polymerization and CD28 signaling functions.
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, 00185 Rome, Italy;
authors.forename: Michela
authors.initials: M
authors.lastname: Muscolini
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, 00185 Rome, Italy;
authors.forename: Cristina
authors.initials: C
authors.lastname: Camperio
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, 00185 Rome, Italy;
authors.forename: Nicla
authors.initials: N
authors.lastname: Porciello
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, 00185 Rome, Italy;
authors.forename: Silvana
authors.initials: S
authors.lastname: Caristi
authors.affiliation: Department of Experimental Medicine, Sapienza University, 00185 Rome, Italy;
authors.forename: Cristina
authors.initials: C
authors.lastname: Capuano
authors.affiliation: The Venetian Institute of Molecular Medicine, Padova 35129, Italy; and Department of Biomedical Sciences, University of Padova, Padova 35121, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Viola
authors.affiliation: Department of Experimental Medicine, Sapienza University, 00185 Rome, Italy;
authors.forename: Ricciarda
authors.initials: R
authors.lastname: Galandrini
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, 00185 Rome, Italy; loretta.tuosto@uniroma1.it.
authors.forename: Loretta
authors.initials: L
authors.lastname: Tuosto
mesh_terms: D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication; D002460:Cell Line; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D009154:Mutation; D015513:Oncogene Proteins / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D055232:Proline-Rich Protein Domains; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens; C078332:Nck protein; D015513:Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase