International Immunology Advance Access originally published online on March 4, 2005
International Immunology 2005 17(4):449-458; doi:10.1093/intimm/dxh225
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CD44 cross-linking induces protein kinase C-regulated migration of human T lymphocytes
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
Correspondence to: Y. Volkov; E-mail: yvolkov{at}tcd.ie
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, ß 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. PKCß 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 ß 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.
Keywords: microtubules, protein kinase C, T cell
* These authors contributed equally to this work.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Y. W. Bourguignon, C. C. Spevak, G. Wong, W. Xia, and E. Gilad Hyaluronan-CD44 Interaction with Protein Kinase C{epsilon} Promotes Oncogenic Signaling by the Stem Cell Marker Nanog and the Production of MicroRNA-21, Leading to Down-regulation of the Tumor Suppressor Protein PDCD4, Anti-apoptosis, and Chemotherapy Resistance in Breast Tumor Cells J. Biol. Chem., September 25, 2009; 284(39): 26533 - 26546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. K. Verma, J. Dourlat, A. M. Davies, A. Long, W.-Q. Liu, C. Garbay, D. Kelleher, and Y. Volkov STAT3-Stathmin Interactions Control Microtubule Dynamics in Migrating T-cells J. Biol. Chem., May 1, 2009; 284(18): 12349 - 12362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. Y. Wong, J. C. Y. Lai, D. Birkenhead, A. S. Shaw, and P. Johnson CD45 Down-Regulates Lck-Mediated CD44 Signaling and Modulates Actin Rearrangement in T Cells J. Immunol., November 15, 2008; 181(10): 7033 - 7043. [Abstract] [Full Text] [PDF]
|
|