title: Type II phosphatidylinositol 4-kinase β is an integral signaling component of early T cell activation mechanisms.
abstract: The early signaling events in T cell activation through CD3 receptor include a rapid change in intra cellular free calcium concentration and reorganization of actin cytoskeleton. Phosphatidylinositol 4-kinases (PtdIns 4-kinases) are implicated as key components in these early signaling events. The role of type II PtdIns 4-kinase β in CD3 receptor signaling was investigated with the help of short hairpin RNA sequences. Cross-linking of CD3 receptors on Jurkat T Cells with monoclonal antibodies showed an early increase in type II PtdIns 4-kinase activity and co-localization of type II PtdIns 4-kinase β with CD3 ζ. Transfection of Jurkat T Cells with shRNAs inhibited CD3 receptor mediated type II PtdIns 4-kinase activation with a concomitant reduction in intra cellular calcium release, suggesting a role for type II PtdIns 4-kinase β in CD3 receptor signal transduction. Knock-down of type II PtdIns 4-kinase β with shRNAs also correlated with a decrease in PtdIns 4-kinase activity in cytoskeleton fractions and reduced adhesion to matrigel surfaces. These results indicate that type II PtdIns 4-kinase β is a key component in early T cell activation signaling cascades.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Wadhwani Research Centre for Biosciences and Bioengineering, Powai, Mumbai, India. ranjeet@scripps.edu
authors.forename: Ranjeet K
authors.initials: RK
authors.lastname: Sinha
authors.forename: Naveen
authors.initials: N
authors.lastname: Bojjireddy
authors.forename: Dakshayini
authors.initials: D
authors.lastname: Kulkarni
authors.forename: Aparna
authors.initials: A
authors.lastname: Ratheesh
authors.forename: S V
authors.initials: SV
authors.lastname: Chiplunkar
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gude
authors.forename: Gosukonda
authors.initials: G
authors.lastname: Subrahmanyam
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D002448:Cell Adhesion; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology*; D018613:Microscopy, Confocal; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology
chemical_list: D017252:CD3 Complex; D019870:1-Phosphatidylinositol 4-Kinase