Human immunodeficiency virus type 1 Nef and p56lck protein-tyrosine kinase interact with a common element in CD4 cytoplasmic tail.
Human immunodeficiency virus type 1 Nef and p56lck protein-tyrosine kinase interact with a common element in CD4 cytoplasmic tail.
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人类免疫缺陷病毒 1 型 Nef 和 p56lck 蛋白酪氨酸激酶与 CD4 细胞质尾部的一个共同元件相互作用。
DOI：
10.1073/pnas.92.2.349
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发表时间：
1995
影响因子：
11.1
通讯作者：
Skowronski,J
中科院分区：
文献类型：
--
作者：
Salghetti,S;Mariani,R;Skowronski,J
人类免疫缺陷病毒1型nef基因诱导CD4抗原内吞并破坏CD4与p56lck蛋白酪氨酸激酶之间的关联（EC 2.7.1.112）。我们证明，在T细胞中，病毒蛋白的这些作用需要在CD4细胞质尾部的膜近端区域有一簇疏水氨基酸；CD4细胞质尾部c端段的其他氨基酸也参与了相互作用。阻止Nef下调的CD4突变也会降低CD4与p56lck的关联，并阻止Nef诱导的CD4-p56lck复合物的破坏。总之，与Nef和p56lck相互作用所需的CD4序列重叠，以及Nef诱导的CD4下调与CD4-p56lck关联破坏之间的密切相关性表明，Nef或Nef募集的细胞因子与这段CD4相互作用，将p56lck从复合物中移出，并诱导CD4内吞作用。
The human immunodeficiency virus type 1 nef gene induces endocytosis of CD4 antigen and disrupts the association between CD4 and p56lck protein-tyrosine kinase (EC 2.7.1.112). We demonstrate that in T cells these effects of the viral protein require a cluster of hydrophobic amino acids in a membrane-proximal region of the CD4 cytoplasmic tail; other amino acids in the C-terminal segment of CD4 cytoplasmic tail also contribute to the interaction. Mutations in CD4 that prevent down-modulation by Nef also decrease CD4 association with p56lck and prevent Nef-induced disruption of CD4-p56lck complexes. Together, the overlap in CD4 sequences required for interaction with Nef and p56lck and the tight correlation between Nef-induced CD4 down-modulation and disruption of CD4-p56lck association suggest that Nef, or cellular factors recruited by Nef, interact with this segment of CD4 to displace p56lck from the complex and induce CD4 endocytosis.