Ravichandran K S, Collins T L, Burakoff S J
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Curr Top Microbiol Immunol. 1996;205:47-62. doi: 10.1007/978-3-642-79798-9_3.
The CD4 molecule plays an important role in the development of CD4+T lymphocytes and it also acts as a coreceptor to enhance responses mediated via the TCR. It is now established that CD4 functions both as an adhesion molecule favoring the T cell: APC interaction and as a signaling molecule. The coreceptor function mediated via CD4 depends on its association with Lck, a src-family tyrosine kinase. Lck, while interacting via its unique NH2-terminal domain with CD4, also interacts via its SH2 and SH3 domains with other intracellular signaling proteins. Although the Lck association with CD4 is essential for CD4 coreceptor activity, the tyrosine kinase activity of CD4-associated Lck appears to be dispensable for CD4 function. Given the necessity of Lck kinase activity for T lymphocyte development and for mature T cell functions, perhaps Lck may function at different stages during T cell activation and at some stages the kinase activity of Lck may not be necessary. This raises an intriguing possibility that CD4-associated Lck may function more as an adapter protein than a kinase and may help to recruit other signaling proteins into the TCR/CD3 complex. However, determination of the precise role of Lck in CD4 coreceptor activity and the domains of Lck that are necessary for CD4-dependent and CD4-independent functions awaits further experiments.
CD4分子在CD4+T淋巴细胞的发育过程中发挥着重要作用，它还作为共受体增强经由TCR介导的反应。现已证实，CD4既作为促进T细胞与抗原呈递细胞（APC）相互作用的黏附分子，又作为信号分子发挥作用。经由CD4介导的共受体功能取决于它与Lck（一种src家族酪氨酸激酶）的结合。Lck在通过其独特的NH2末端结构域与CD4相互作用时，还通过其SH2和SH3结构域与其他细胞内信号蛋白相互作用。尽管Lck与CD4的结合对于CD4共受体活性至关重要，但与CD4相关的Lck的酪氨酸激酶活性对于CD4功能似乎并非必需。鉴于Lck激酶活性对于T淋巴细胞发育和成熟T细胞功能的必要性，或许Lck可能在T细胞活化的不同阶段发挥作用，而在某些阶段Lck的激酶活性可能并非必需。这就引发了一种有趣的可能性，即与CD4相关的Lck可能更多地作为衔接蛋白而非激酶发挥作用，并可能有助于将其他信号蛋白招募到TCR/CD3复合物中。然而，确定Lck在CD4共受体活性中的精确作用以及Lck对于依赖CD4和不依赖CD4功能所必需的结构域，仍有待进一步实验。
