PI 3-kinase sub-pathways in lymphocyte activation: regulation and functions of phosphatidylinositol (3,4)-bisphosphate

Abstract

Event Abstract Back to Event PI 3-kinase sub-pathways in lymphocyte activation: regulation and functions of phosphatidylinositol (3,4)-bisphosphate Aaron J. Marshall1*, Nipun Jayachandran1, Hongzhao Li1, Ivan Landego1, Samantha Pauls1 and Sen Hou1 1 University of Manitoba, Immunology, Canada Activation of PI3-kinase enzymes is essential for lymphocyte development and function. Active PI3Ks generate several types of D3 phosphoinositides (PI), including PI(3,4,5)P3 and PI(3,4)P2. These PIs are under distinct regulation by PI phosphatases, have distinct protein binding partners and distinct functions in cell biology. We are assessing the regulation of the PI(3,4)P2 sub-pathway via phosphatases SHIP1 and INPP4A, as well as the functions of PI(3,4)P2-binding proteins TAPP1, TAPP2, Bam32/DAPP1 and lamellipodin. Function of TAndem PH domain containing Proteins (TAPPs) have been assessed using knock-in mutant mice in which both TAPP1 and TAPP2 are uncoupled from PI(3,4)P2. We found that these TAPP KI mice exhibit elevated serum antibody levels and also develop autoantibodies and kidney pathology resembling that of lupus. TAPP KI B cells show increased responses to BCR stimulation associated with elevated Akt activation. TAPP KI mice show evidence of chronic lymphocyte activation in vivo and generated elevated germinal center (GC) responses upon immunization. We hypothesize that TAPP adaptor binding to PI(3,4)P2 contributes a novel regulatory mechanism controlling B cell activation. We further find that PI(3,4)P2 can positively contributes to some B cell functions, particularly migratory responses to chemokine stimulation. We found that selective degradation of PI(3,4)P2 by INPP4A impairs B cell migration and have implicated PI(3,4)P2-binding proteins TAPP2 and lamellipodin as important regulators of lymphocyte migration. Together these results indicate that distinct PI pathways activated by PI3K contribute to different aspects of B cell activation. Acknowledgements Funding provided by the Canadian Institutes of Health Research and the Canadian Cancer Society. Keywords: B lymphocytes, Signal Transduction, Phosphoinositide 3-kinase, phosphoinositides, Autoimmunity, Leukemia, Lymphoid, germinal centers Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune receptors and signaling Citation: Marshall AJ, Jayachandran N, Li H, Landego I, Pauls S and Hou S (2013). PI 3-kinase sub-pathways in lymphocyte activation: regulation and functions of phosphatidylinositol (3,4)-bisphosphate. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00072 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 08 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Aaron J Marshall, University of Manitoba, Immunology, Winnipeg, MB, R3E-0T5, Canada, aaron.marshall@umanitoba.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Aaron J Marshall Nipun Jayachandran Hongzhao Li Ivan Landego Samantha Pauls Sen Hou Google Aaron J Marshall Nipun Jayachandran Hongzhao Li Ivan Landego Samantha Pauls Sen Hou Google Scholar Aaron J Marshall Nipun Jayachandran Hongzhao Li Ivan Landego Samantha Pauls Sen Hou PubMed Aaron J Marshall Nipun Jayachandran Hongzhao Li Ivan Landego Samantha Pauls Sen Hou Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.