HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print October 31, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0206109v1 81/2/509    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grybko, M. J. Articles by Zweifach, A. Search for Related Content PubMed PubMed Citation Articles by Grybko, M. J. Articles by Zweifach, A.

(Journal of Leukocyte Biology. 2007;81:509-519.)
© 2007 by Society for Leukocyte Biology

Protein kinase C activity is required for cytotoxic T cell lytic granule exocytosis, but the isoform does not play a preferential role

Department of Physiology and Biophysics, University of Colorado Health Sciences Center, Aurora, Colorado, USA

¹ Correspondence at current address: Department of Molecular and Cell Biology, University of Connecticut at Storrs, 91 North Eagleville Road, Storrs, CT 06269-3125. E-mail: adam.zweifach{at}uconn.edu

CTLs kill virus-infected, tumor, and transplanted targets via secretion of lytic agents including perforin and granzymes. Knowledge of the signals controlling this important process remains vague. We have tested the idea that protein kinase C (PKC), a member of the novel PKC (nPKC) family, which has been shown to play a preferential role in critical Th cell functions, plays a similar, preferential role in CTL lytic granule exocytosis using T acute lymphoblastic leukemia-104 (TALL-104) human leukemic CTLs as a model. We provide evidence consistent with the idea that PKC activity is important for the degranulation step of lytic granule exocytosis, as opposed to upstream events. In contrast with previous work, our results with pharmacological agents suggest that conventional PKCs (cPKCs) and nPKCs may participate. Our results suggest that stimulation with soluble agents that bypass the TCR and trigger granule exocytosis activates PKC and PKC, which can both accumulate at the site of contact with a target cell, although PKC did so more often. Finally, using a novel assay that detects granule exocytosis specifically in transfected, viable cells, we find that overexpression of constitutively active mutants of PKC or PKC can synergize with increases in intracellular [Ca²⁺] to promote granule exocytosis. Taken together, our results lend support for the idea that PKC does not play a preferential role in CTL granule exocytosis.

Key Words: cytotoxicity • PKC • flow cytometry

This article has been cited by other articles:

				A. M. Beal, N. Anikeeva, R. Varma, T. O. Cameron, P. J. Norris, M. L. Dustin, and Y. Sykulev Protein Kinase C{theta} Regulates Stability of the Peripheral Adhesion Ring Junction and Contributes to the Sensitivity of Target Cell Lysis by CTL J. Immunol., October 1, 2008; 181(7): 4815 - 4824. [Abstract] [Full Text] [PDF]

				M. J. Grybko, J. P. Bartnik, G. A. Wurth, A. T. Pores-Fernando, and A. Zweifach Calcineurin Activation Is Only One Calcium-dependent Step in Cytotoxic T Lymphocyte Granule Exocytosis J. Biol. Chem., June 22, 2007; 282(25): 18009 - 18017. [Abstract] [Full Text] [PDF]

				J. S. Y. Ma, N. Monu, D. T. Shen, I. Mecklenbrauker, N. Radoja, T. F. Haydar, M. Leitges, A. B. Frey, S. Vukmanovic, and S. Radoja Protein Kinase C{delta} Regulates Antigen Receptor-Induced Lytic Granule Polarization in Mouse CD8+ CTL J. Immunol., June 15, 2007; 178(12): 7814 - 7821. [Abstract] [Full Text] [PDF]