       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).

