CD44 cross-linking induces protein kinase C-regulated migration of human T lymphocytes
Source: International Immunology, Volume 17, Number 4, April 2005 , pp. 449-458(10)
Publisher: Oxford University Press
Abstract:The cell surface receptor CD44 is widely implicated in leukocyte migration to inflammatory sites. In this study, the responses of human T cells following cross-linking of CD44 were examined. We demonstrate that engagement of CD44 using immobilized mAbs or hyaluronan-enriched extracellular matrix lattices induces active migration in T lymphocytes accompanied by cycles of cytoskeletal rearrangement and cell polarization. We have investigated the functional impact and subcellular localization of protein kinase C (PKC) isoenzymes, and , previously shown by our group to be involved in active T cell locomotion induced by leukocyte function-associated antigen-1 (LFA-1) integrin receptors. PKC was associated with the centrosome and the microtubule-rich tail of the polarized cell and PKC was predominantly located about the region of the microtubule organizing center. A selective pharmacological inhibitor of classical PKC isoforms, Gö6976, suppressed lymphocyte polarization and migration following CD44 ligation. Selective targeting of PKC using the pharmacological inhibitor rottlerin or a pseudosubstrate-blocking peptide reduced CD44-activated cell migration but did not completely ablate it. Our data demonstrate that ligation of CD44 induces phenotypic changes, cytoskeletal rearrangements and redistribution of PKC isoforms and , resulting in cell migration, as previously described for the cell surface receptor, LFA-1. This suggests potential convergence of intracellular signaling pathways induced via CD44 and LFA-1 integrin.
Document Type: Research Article
Affiliations: 1: Department of Clinical Medicine, Trinity College, and Dublin Molecular Medicine Centre, James's Street, Dublin 8, Ireland 2: Department of Biochemistry, Royal College of Surgeons of Ireland, Dublin 2, Ireland
Publication date: 2005-04-01
- International Immunology publishes a broad range of experimental and theoretical studies in molecular and cellular immunology conducted in laboratories throughout the world.