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1996-02-26
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Document 0525
DOCN M9620525
TI Immobilized antibodies to CD45 induce rapid morphologic changes and
increased tyrosine phosphorylation of p56lck-associated proteins in T
cells.
DT 9602
AU Arendt CW; Hsi G; Ostergaard HL; Department of Medical Microbiology and
Immunology, University of; Alberta, Edmonton, Canada.
SO J Immunol. 1995 Dec 1;155(11):5095-103. Unique Identifier : AIDSLINE
MED/96072781
AB CD45 is a transmembrane protein tyrosine phosphatase required for signal
transduction through the Ag receptor complexes of T and B lymphocytes.
Herein, we demonstrate that immobilized mAbs to the external domain of
CD45 induce rapid and dramatic morphologic changes in a variety of T
cell lines, including CD8+ cytotoxic clones. CD45-induced morphologic
changes can be inhibited by the cytoskeletal inhibitors cytochalasin D
and E and by the protein tyrosine kinase inhibitor herbimycin A.
Consistent with the requirement for tyrosine kinase activity, tyrosine
phosphorylation of proteins at about 60 to 75 kDa and 115 to 130 kDa is
increased upon engagement with immobilized anti-CD45 mAb with kinetics
paralleling the observed changes in morphology. The phosphorylation of
these proteins is inhibited by tyrosine kinase inhibitors at
concentrations that also inhibit changes in morphology. The
phosphoproteins induced when cells are added to immobilized anti-CD45
are co-immunoprecipitated with p56lck, suggesting that this tyrosine
kinase might play a role in the phosphorylation of these proteins.
Consistent with this, there is no increase in the phosphorylation of
these proteins in p56lck-deficient CTLL-2 cells in response to
immobilized anti-CD45 mAb. An important role for p56lck in the
morphologic pathway is further supported by the observation that
p56lck-deficient human J.CAM1.6 cells, in contrast to the parental
Jurkat line, cannot be induced to undergo morphologic changes. Taken
together, these results suggest a possible role for CD45 in coordinating
a cytoskeletal remodeling cascade that may be important in cell
activation.
DE src-Family Kinases/*METABOLISM Actins/ANTAGONISTS & INHIB/METABOLISM
Animal Antibodies, Monoclonal/*IMMUNOLOGY/METABOLISM Antigens,
CD3/IMMUNOLOGY Antigens, CD45/*IMMUNOLOGY Cytoskeleton/DRUG
EFFECTS/METABOLISM CD8-Positive T-Lymphocytes/*IMMUNOLOGY/PATHOLOGY
Enzyme Inhibitors/PHARMACOLOGY Hybridomas Lymphocyte Transformation
Mice Phosphorylation Quinones/PHARMACOLOGY Signal Transduction/DRUG
EFFECTS Support, Non-U.S. Gov't Tumor Cells, Cultured JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).