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Inhibition of tyrosine kinase activation blocks the down-regulation of CXC chemokine receptor 4 by HIV-1 gp120 in CD4(+) T cells

  1. Author:
    Su, S. B.
    Gong, W. H.
    Grimm, M.
    Utsunomiya, I.
    Sargeant, R.
    Oppenheim, J. J.
    Wang, J. M.
  2. Author Address

    Wang JM NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Immunogenet Mol Lab Bldg 560,Room 31-19 Frederick, MD 21702 USA NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Immunogenet Mol Lab Frederick, MD 21702 USA NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, MD 21702 USA Millenium Biotechnol Ramona, CA 92065 USA
    1. Year: 1999
  1. Journal: Journal of Immunology
    1. 162
    2. 12
    3. Pages: 7128-7132
  2. Type of Article: Article
  1. Abstract:

    Because the binding of HIV-1 envelope to CD4 initiates a cofigurational change in glycoprotein 120 (gp120), enabling it to interact with fusion coreceptors, we investigated how this process interferes with the expression and function of CXC chemokine receptor 4 (CXCR4) in CD4(+) T lymphocytes, A recombinant gp120 (MN), after preincubation with CD4(+) T lymphocytes, significantly inhibited the binding and chemotaxis of the cells in response to the CXCR4 ligand stromal cell-derived factor-1 alpha (SDF-1 alpha), accompanied by a markedly reduced surface expression of CXCR4, gp120, but not SDF-1 alpha, induced rapid tyrosine phosphorylation of src-like kinase p56(lck) in CD4(+) T cells, whereas both gp120 and SDF-1 alpha caused phosphorylation of the CXCR4, The tyrosine kinase inhibitor herbimycin A abolished the phosphorylation of p56(lck) and CXCR4 induced by gp120 in association with maintenance of normal expression of cell surface CXCR4 and a migratory response to SDF-1 alpha, Thus, a CD4-associated signaling molecule(s) including p56(lck) is activated by gp120 and is required for the down-regulation of CXCR4. [References: 30]

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