TY - JOUR
T1 - Inhibition of tyrosine kinase activation blocks the down-regulation of CXC chemokine receptor 4 by HIV-1 gp120 in CD4+ T cells
AU - Su, Shao Bo
AU - Gong, Wanghua
AU - Grimm, Michael
AU - Utsunomiya, Iku
AU - Sargeant, Robert
AU - Oppenheim, Joost J.
AU - Wang, Ji Ming
PY - 1999/6/15
Y1 - 1999/6/15
N2 - Because the binding of HIV-1 envelope to CD4 initiates a configurational 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-1α (SDF-1α), accompanied by a markedly reduced surface expression of CXCR4. gp120, but not SDF-1α, induced rapid tyrosine phosphorylation of src-like kinase p56(lck) in CD4+ T cells, whereas both gp120 and SDF-1α 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-1α. Thus, a CD4-associated signaling molecule(s) including p56(lck) is activated by gp120 and is required for the down-regulation of CXCR4.
AB - Because the binding of HIV-1 envelope to CD4 initiates a configurational 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-1α (SDF-1α), accompanied by a markedly reduced surface expression of CXCR4. gp120, but not SDF-1α, induced rapid tyrosine phosphorylation of src-like kinase p56(lck) in CD4+ T cells, whereas both gp120 and SDF-1α 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-1α. Thus, a CD4-associated signaling molecule(s) including p56(lck) is activated by gp120 and is required for the down-regulation of CXCR4.
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M3 - Article
C2 - 10358157
AN - SCOPUS:0010115325
SN - 0022-1767
VL - 162
SP - 7128
EP - 7132
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -