HIV glycoprotein gp120 inhibits TCR-CD3-mediated activation of fyn and lck.
HIV glycoprotein gp120 inhibits TCR-CD3-mediated activation of fyn and lck.
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HIV 糖蛋白 gp120 抑制 TCR-CD3 介导的 fyn 和 lck 激活。
DOI：
10.1093/intimm/9.1.53
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发表时间：
1997
影响因子：
4.4
通讯作者：
Geha,RS
中科院分区：
文献类型：
--
作者：
Morio,T;Chatila,T;Geha,RS
HIV主要糖蛋白gp 120与CD 4分子相互作用并通过TCR-CD 3复合物干扰信号传导。我们研究了gp 120对TCR-CD 3诱导的src型蛋白酪氨酸激酶（PTK）fyn和lck的磷酸化和活化的影响。gp 120引起lck磷酸化或lck酶活性的最小变化，但用gp 120预孵育Jurkat细胞20分钟强烈抑制TCR-CD 3介导的lck和fyn的磷酸化和活化，以及CD 3 zeta的磷酸化。用gp 120预孵育的T细胞中TCR-CD 3信号传导的抑制通过抑制T细胞对抗原破伤风类毒素的增殖来消除。gp 120既不影响表面CD 4表达，也不影响CD 4-lck结合。此外，gp 120抑制由TCR-CD 3和CD 4交联诱导的lck磷酸化，这表明lck磷酸化的抑制不能简单地通过螯合CD 4分子来解释。相对于含有正调节残基Tyr 394的lck肽，gp 120选择性地增强含有自身抑制性酪氨酸残基Tyr 505的lck肽的磷酸化，这表明lck的定性改变可能是gp 120抑制TCR-CD 3信号传导的基础。
HIV major glycoprotein gp120 interacts with CD4 molecules and perturbs signaling through the TCR-CD3 complex. We examined the effects of gp120 on TCR-CD3-induced phosphorylation and activation of the src-type protein tyrosine kinases (PTK), fyn and lck. gp120 caused minimal changes in lck phosphorylation or lck enzymatic activity, but preincubation of Jurkat cells with gp120 for 20 min strongly inhibited TCR-CD3-mediated phosphorylation and activation of lck and fyn, as well as phosphorylation of CD3 zeta. Inhibition of TCR-CD3 signaling in T cells preincubated with gp120 was paralleled by inhibition of T cell proliferation to the antigen tetanus toxoid. Neither surface CD4 expression nor CD4-lck association was affected by gp120. Furthermore, gp120 inhibited lck phosphorylation induced by cross-linking of TCR-CD3 and CD4 suggesting that the inhibition of lck phosphorylation could not be simply accounted for by sequestration of CD4 molecules. gp120 selectively enhanced the phosphorylation of the lck peptide containing the autoinhibitory tyrosine residue Tyr505 relative to the lck peptide containing the positive regulatory residue Tyr394, suggesting that a qualitative alteration in lck may underlie the inhibition of TCR-CD3 signaling by gp120.