Bacon C M, McVicar D W, Ortaldo J R, Rees R C, O'Shea J J, Johnston J A
Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.
J Exp Med. 1995 Jan 1;181(1):399-404. doi: 10.1084/jem.181.1.399.
Interleukin (IL-12) has many effects on the function of natural killer and T cells, and is important in the control of cell-mediated immunity. IL-2 and IL-12 display many similar activities, yet each also induces a distinct set of responses. A human IL-12 receptor subunit has recently been cloned and, like the IL-2R beta and IL-2R gamma, is a member of the hematopoietic receptor superfamily; however, the molecular mechanisms of IL-12 action are unknown. In this report we show that IL-12 and IL-2 induce tyrosine phosphorylation of distinct members of the Janus (JAK) family of protein tyrosine kinases in human T lymphocytes. IL-12, but not IL-2, stimulates the tyrosine phosphorylation of TYK2 and JAK2, whereas JAK1 and JAK3, which are phosphorylated in response to IL-2, are not phosphorylated after IL-12 treatment. The use of distinct but related JAK family tyrosine kinases by IL-12 and IL-2 may provide a biochemical basis for their different biological activities.
白细胞介素（IL-12）对自然杀伤细胞和T细胞的功能有多种影响，在细胞介导的免疫控制中起重要作用。IL-2和IL-12表现出许多相似的活性，但它们各自也诱导出一组不同的反应。最近克隆了一种人IL-12受体亚基，它与IL-2Rβ和IL-2Rγ一样，是造血受体超家族的成员；然而，IL-12作用的分子机制尚不清楚。在本报告中，我们表明IL-12和IL-2在人T淋巴细胞中诱导Janus（JAK）家族蛋白酪氨酸激酶的不同成员发生酪氨酸磷酸化。IL-12能刺激TYK2和JAK2的酪氨酸磷酸化，但IL-2不能，而对IL-2有反应而发生磷酸化的JAK1和JAK3在IL-12处理后未发生磷酸化。IL-12和IL-2使用不同但相关的JAK家族酪氨酸激酶可能为它们不同的生物学活性提供生化基础。
