Epitope-specific crosslinking of CD45 down-regulates membrane-associated tyrosine phosphatase activity and triggers early signalling events in human activated T cells.
Details
Serval ID
serval:BIB_E13DFA233C41
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Epitope-specific crosslinking of CD45 down-regulates membrane-associated tyrosine phosphatase activity and triggers early signalling events in human activated T cells.
Journal
Immunology
ISSN
0019-2805[print], 0019-2805[linking]
Publication state
Published
Issued date
2004
Volume
113
Number
4
Pages
441-452
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
CD45 engagement by monoclonal antibodies on human activated T cells triggers tumour necrosis factor-alpha (TNF-alpha) gene transcription in an epitope-specific manner. To dissect the early signalling events leading to TNF-alpha gene expression, we established that CD45 crosslinking resulted in tyrosine phosphorylation of p56lck, ZAP-70, CD3-zeta, LAT and Vav. This was accompanied by down-regulation of membrane-associated protein tyrosine phosphatase activity in the absence of demonstration of enhanced p56lck, p72syk and ZAP-70 kinase activity, which remained constitutive. These early events eventually triggered an intracellular Ca(2+) rise and phosphoinositide turnover. We conclude that down-regulation of membrane-associated tyrosine phosphatase activity by CD45 extracytoplasmic domain multimerization led, in an epitope-specific fashion, to unopposed tyrosine kinase activity and to the activation of the T-cell receptor/CD3 complex signalling cascade, resulting in TNF-alpha gene expression. This model strongly suggests that CD45 extracytoplasmic tail multimerization may contribute to the modulation T-cell functions.
Keywords
Antigens, CD45/immunology, Cells, Cultured, Down-Regulation/immunology, Epitopes, T-Lymphocyte/immunology, Humans, Lymphocyte Activation/immunology, Phosphorylation, Protein Tyrosine Phosphatases/metabolism, Signal Transduction/immunology, T-Lymphocytes/immunology, Tumor Necrosis Factor-alpha/biosynthesis, Tumor Necrosis Factor-alpha/genetics
Pubmed
Web of science
Create date
25/01/2008 15:53
Last modification date
20/08/2019 17:05