       Document 0733
 DOCN  M9610733
 TI    The protein tyrosine kinase p56lck regulates TCR expression and T cell
       selection.
 DT    9601
 AU    Ericsson PO; Teh HS; Department of Microbiology and Immunology,
       University of British; Columbia, Vancouver, Canada.
 SO    Int Immunol. 1995 Apr;7(4):617-24. Unique Identifier : AIDSLINE
       MED/96031359
 AB    The role of the protein tyrosine kinase (PTK), p56lck, in T cell
       development was evaluated by mating TCR transgenic mice with transgenic
       mice that expressed lckF505, a constitutively activated form of p56lck
       which is under the control of the lck proximal promoter element. The TCR
       transgenic mice expressed either a receptor specific for the male
       antigen presented by Db (H-Y TCR) or a receptor specific for pigeon
       cytochrome c peptide presented by I-Ek class II MHC molecules (AND TCR).
       The lckF505 transgene caused lower TCR expression in immature CD4+CD8+
       thymocytes from normal and TCR transgenic mice. Consistent with the
       conclusion that activated p56lck causes lower TCR expression, the PTK
       inhibitor, herbimycin A, was able to restore TCR expression to normal
       levels in CD4+CD8+ thymocytes from TCR/lckF505 doubly transgenic mice.
       However, despite lower TCR expression, calcium mobilization was only
       moderately reduced in CD4+CD8+ thymocytes from H-Y TCR/lckF505 doubly
       transgenic mice. Furthermore, negative selection of CD4+CD8+ thymocytes
       expressing the H-Y TCR occurred efficiently in H-Y TCR/lckF505 doubly
       transgenic male mice despite lower TCR levels. By contrast, analysis of
       H-Y TCR/lckF505 and AND TCR/lckF505 doubly transgenic mice showed that
       positive selection in these mice was reduced by 4- to 5-fold by the
       lckF505 transgene. The smaller proportion of cells that were positively
       selected in doubly transgenic lckF505 mice expressed normal levels of
       TCR but higher levels of the appropriate CD4 or CD8 co-receptor
       molecule. These results indicate that the positive selection of
       thymocytes is regulated by the enzymatic activity of p56lck.
 DE    src-Family Kinases/GENETICS/*PHYSIOLOGY  Animal  Calcium/METABOLISM
       Cell Differentiation/IMMUNOLOGY  CD4-Positive T-Lymphocytes/METABOLISM
       CD8-Positive T-Lymphocytes/METABOLISM  Female  Male  Mice  Mice, Inbred
       C57BL  Mice, Transgenic  Protein-Tyrosine Kinase/ANTAGONISTS & INHIB
       Quinones/PHARMACOLOGY  Receptor-CD3 Complex, Antigen,
       T-Cell/BIOSYNTHESIS/GENETICS  Receptors, Antigen,
       T-Cell/*BIOSYNTHESIS/GENETICS/PHYSIOLOGY  Support, Non-U.S. Gov't
       T-Lymphocytes/IMMUNOLOGY/*METABOLISM  Transgenes/PHYSIOLOGY  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

