Document 0265
 DOCN  M9590265
 TI    Interleukin-2 receptor beta-chain signal transduction: implications for
       HIV immunopathogenesis.
 DT    9509
 AU    Williamson P; Merida I; Gaulton G; Department of Immunology, Westmead
       Hospital.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:257 (unnumbered poster).
       Unique Identifier : AIDSLINE ASHM6/95291834
 AB    Interleukin-2 (IL-2) is a major growth and differentiation factor for
       T-cells, B-cells, NK-cells and monocytes. HIV infection is associated
       with abnormalities in IL-2 production and IL-2 responsiveness, which in
       turn are largely responsible for T-cell functional defects. Despite
       potential importance to HIV immunopathogenesis, growth and
       differentiation signalling mechanisms induced by IL-2, and mediated
       through the heterotrimeric IL-2 receptor (IL-2R) complex, are still
       being defined. The beta-chain subunit is essential for formation of
       intermediate and high affinity receptors, and is required for
       signalling. IL-2R beta has a 286 amino acid cytoplasmic domain in which
       two regions, the S-region and A-region, have been implicated in signal
       transduction. To examine the molecular interactions involved in IL-2
       dependent signalling, we have studied the role of IL-2R beta subregions
       using a series of IL-2R beta chain mutants transfected into the pro-B
       cell line Baf-B03. Using these mutants we have identified an IL-2R beta
       functional domain that is responsible for activation of tyrosine kinase
       and phosphatidylinositol 3-kinase activities. The results also suggest
       that src-kinase family members interact with IL-2R beta between amino
       acid residues 323 and 350. Despite activation of these kinases the cells
       were not able to proliferate in response to IL-2, unless complemented by
       transfection of a myc gene. The implications of these studies for HIV
       immunopathogenic mechanisms will be discussed.
 DE    Cell Line  Enzyme Activation/GENETICS  Human  HIV/GENETICS/IMMUNOLOGY
       HIV Infections/*IMMUNOLOGY  Interleukin-2/*BIOSYNTHESIS  Lymphocyte
       Transformation/GENETICS/IMMUNOLOGY  Lymphocytes/IMMUNOLOGY  Mutation
       Phosphotransferases (Alcohol Group Acceptor)/METABOLISM
       Protein-Tyrosine Kinase/METABOLISM  Receptors,
       Interleukin-2/GENETICS/*IMMUNOLOGY  Signal
       Transduction/GENETICS/*IMMUNOLOGY  Transfection  MEETING ABSTRACT

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       protected by Copyright Law (Title 17, U.S.Code).