Repke H, Barber E, Ulbricht S, Buchner K, Hucho F, Kopp R, Scholz H, Rudd C E, Haseltine W A
Division of Human Retrovirology, Dana Farber Cancer Institute, Boston, MA 02115.
J Immunol. 1992 Oct 15;149(8):2585-91.
Gangliosides induce a selective and complete modulation of CD4 from the surface of T cells. CD4 down-modulation occurs by CD4 endocytosis. This process is independent of serine phosphorylation of the cytoplasmic tail of CD4 and does not require the association between the tyrosine protein kinase p56lck and the cytoplasmic tail of CD4. Ganglioside-induced CD4 endocytosis is accompanied by the loss of p56lck activity associated with CD4. Sequential immunoprecipitation analysis using an anti-CD4 antibody and an anti-p56lck antiserum showed that this is caused by the dissociation of the enzyme from the cytoplasmic tail of CD4. The kinetics of p56lck dissociation after ganglioside treatment is identical to that of CD4 endocytosis, suggesting that p56lck is displaced in the process of endosome formation. The results indicate that CD4 endocytosis alone can cause the dissociation of the p56lck complex without the requirement for CD4 phosphorylation.
神经节苷脂可诱导T细胞表面CD4发生选择性且完全的调节。CD4的下调是通过CD4的内吞作用实现的。这一过程不依赖于CD4胞质尾部的丝氨酸磷酸化，也不需要酪氨酸蛋白激酶p56lck与CD4胞质尾部之间的结合。神经节苷脂诱导的CD4内吞作用伴随着与CD4相关的p56lck活性的丧失。使用抗CD4抗体和抗p56lck抗血清进行的顺序免疫沉淀分析表明，这是由于该酶从CD4胞质尾部解离所致。神经节苷脂处理后p56lck解离的动力学与CD4内吞作用的动力学相同，表明p56lck在内体形成过程中被取代。结果表明，仅CD4内吞作用就能导致p56lck复合物的解离，而无需CD4磷酸化。
