CD44 signaling through p56lck involves lateral association with CD4 in human CD4+ T cells
| Autor: | Antonella Tosti, Manuela Bragardo, Umberto Dianzani, Sara Bonissoni, María José Feito, Myriam Casucci, Andrea Velardi, Flavia Bottarel, Loredana Ruggeri, Isabella Volpi |
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| Rok vydání: | 1999 |
| Předmět: |
CD4-Positive T-Lymphocytes
CD3 Immunology Lymphocyte Activation Humans Immunology and Allergy Phosphorylation Phytohemagglutinins ZAP-70 Protein-Tyrosine Kinase biology Phospholipase C Phospholipase C gamma CD44 Alternative splicing General Medicine Protein-Tyrosine Kinases Precipitin Tests Cell biology Enzyme Activation Isoenzymes Hyaluronan Receptors Membrane protein Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Type C Phospholipases Phosphoprotein CD4 Antigens biology.protein Signal transduction Signal Transduction |
| Zdroj: | International Immunology. 11:1085-1092 |
| ISSN: | 1460-2377 0953-8178 |
| DOI: | 10.1093/intimm/11.7.1085 |
| Popis: | CD44 is a family of mucin-like membrane proteins generated by alternative splicing of several exons, and participate in T cell adhesion and activation. CD44-mediated signaling involves activation of p56(lck) and leads to ZAP-70 phosphorylation. The aim of the present study was to identify the signaling pathways that follow CD44-triggered ZAP-70 phosphorylation and the molecular mechanisms underlying the CD44 interaction with p56(lck). We found that CD44 cross-linking by mAb in CD4(+) peripheral blood T cells promotes formation of a trimeric complex of Grb2, phospholipase (PLC)-gamma1 and a 36-38 kDa phosphoprotein, and the activation of PLC-gamma1. The amount of inositol triphosphate and the time kinetics of its generation were comparable to those following CD3 cross-linking. Co-capping, co-immunoprecipitation and fluorescence resonance energy transfer experiments showed that CD44 associates with CD4 and CD3 on the cell surface. This association suggests functional interplay between the CD4-TCR complex and CD44. In line with this possibility, we found that CD4 triggering by gp120, a natural ligand of CD4, potentiates CD44-mediated adhesion to hyaluronic acid. Moreover, Ca2+ mobilization induced by CD44 cross-linking by mAb was higher in a subclone of the HUT78 cell line expressing CD4 than in a non-expressing subclone. |
| Databáze: | OpenAIRE |
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