Corbeil J, Tremblay M, Richman D D
Department of Medicine, University of California, San Diego, La Jolla 92093-0679, USA.
J Exp Med. 1996 Jan 1;183(1):39-48. doi: 10.1084/jem.183.1.39.
The roles of the CD4 receptor and the src kinase p56lck were examined in the process of HIV-induced apoptosis of CD4+ T lymphocytes. The presence of the CD4 cytoplasmic tail was found to be essential in delivering an apoptotic signal, and interaction of CD4 with p56lck potentiated HIV-induced apoptosis. Apoptosis, but not HIV replication, was abrogated by deleting the NH2-terminal intracytoplasmic tail of CD4, or by mutating the two critical cysteines in this tail that are responsible for CD4-p56lck interaction. Introduction of p56lck in C8166-45 or MT-2 cells, CD4+ T cell lines deficient for this protein, greatly increased HIV-induced apoptosis and syncytium formation. The ability of p56lck to deliver an apoptotic signal did not depend on its kinase function, since a kinase-deficient mutant was as effective as its normal counterpart in inducing apoptosis, suggesting that p56lck may act as an adapter to anchor other proteins to transduce the death signal.
在HIV诱导CD4+ T淋巴细胞凋亡的过程中，对CD4受体和src激酶p56lck的作用进行了研究。发现CD4细胞质尾巴的存在对于传递凋亡信号至关重要，并且CD4与p56lck的相互作用增强了HIV诱导的凋亡。通过删除CD4的NH2末端胞质尾巴，或通过突变该尾巴中负责CD4 - p56lck相互作用的两个关键半胱氨酸，可消除凋亡，但不影响HIV复制。在C8166 - 45或MT - 2细胞（缺乏该蛋白的CD4+ T细胞系）中引入p56lck，可大大增加HIV诱导的凋亡和多核巨细胞形成。p56lck传递凋亡信号的能力并不依赖于其激酶功能，因为激酶缺陷型突变体在诱导凋亡方面与正常对应物一样有效，这表明p56lck可能作为一种衔接蛋白，将其他蛋白锚定以转导死亡信号。
