Spatial and temporal regulation of protein kinase D (PKD)
Sharon A. Matthews,
Teresa Iglesias1,
Enrique Rozengurt2, and
Doreen Cantrell3
Lymphocyte Activation Laboratory and 1Molecular Neuropathobiology Laboratory, Imperial Cancer Research Fund, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK and 2Department of Medicine, UCLA School of Medicine and Molecular Biology Institute, 900 Veteran Avenue, Warren Hall, Los Angeles, CA 90095-1786, USA 3Corresponding author e-mail: d.cantrell{at}icrf.icnet.uk
Abstract:
Protein kinase D (PKD; also known as PKCµ) is a serine/threonine kinase activated by diacylglycerol signalling pathways in a variety of cells. PKD has been described previously as Golgi-localized, but herein we show that it is present within the cytosol of quiescent B cells and mast cells and moves rapidly to the plasma membrane after antigen receptor triggering. The membrane redistribution of PKD requires the diacylglycerol-binding domain of the enzyme, but is independent of its catalytic activity and does not require the integrity of the pleckstrin homology domain. Antigen receptor signalling initiates in glycosphingolipid-enriched microdomains, but membrane-associated PKD does not co-localize with these specialized structures. Membrane targeting of PKD is transient, the enzyme returns to the cytosol within 10 min of antigen receptor engagement. Strikingly, the membrane-recycled PKD remains active in the cytosol for several hours. The present work thus characterizes a sustained antigen receptor-induced signal transduction pathway and establishes PKD as a serine kinase that temporally and spatially disseminates antigen receptor signals away from the plasma membrane into the cytosol.
Key Words: Keywords: antigen receptor/cysteine-rich domain/diacylglycerol/PKCµ/PKD
