Musso T, Johnston J A, Linnekin D, Varesio L, Rowe T K, O'Shea J J, McVicar D W
Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, Frederick, Maryland 21702-1201, USA.
J Exp Med. 1995 Apr 1;181(4):1425-31. doi: 10.1084/jem.181.4.1425.
The Janus family of kinases (JAKs) has been shown to be involved in the signal transduction of a number of cytokine receptors. Recently, we have cloned a novel JAK family member, JAK3, that is expressed in natural killer and activated T cells and is coupled functionally and physically to the interleukin 2 (IL-2) receptor in these cells. Here we report that JAK3 was expressed at low but detectable levels in human monocytes. In contrast, JAK3 expression was strongly induced during activation by interferon gamma (IFN-gamma) or lipopolysaccharide. Moreover, JAK3 became tyrosine phosphorylated in response to IL-2, IL-4, and IL-7 but not response to IFN-gamma or granulocyte/macrophage colony-stimulating factor. Together, these findings suggest that JAK3 is functionally important in activated monocytes and cells of the myeloid lineage and is involved in signaling responses of cytokines that use the common gamma-chain of the IL-2 receptor.
已证实酪氨酸激酶(JAK)家族参与多种细胞因子受体的信号转导。最近,我们克隆了一个新的JAK家族成员JAK3,它在自然杀伤细胞和活化的T细胞中表达,并在这些细胞中与白细胞介素2(IL-2)受体在功能和物理上相偶联。在此我们报告,JAK3在人单核细胞中以低水平但可检测到的水平表达。相比之下,在γ干扰素(IFN-γ)或脂多糖激活过程中,JAK3表达被强烈诱导。此外,JAK3在受到IL-2、IL-4和IL-7刺激时发生酪氨酸磷酸化,但对IFN-γ或粒细胞/巨噬细胞集落刺激因子无反应。这些发现共同表明,JAK3在活化的单核细胞和髓系谱系细胞中具有重要功能,并且参与使用IL-2受体共同γ链的细胞因子的信号转导反应。