Yoshimura A
Institute of Life Science, Kurume University, Japan.
Leukemia. 1998 Dec;12(12):1851-7. doi: 10.1038/sj.leu.2401238.
A family of cytokine-inducible SH2 proteins (CISs) has recently been identified and the number of family members is growing. In this family, the central SH2 domain and C-terminal (about 40 amino acids) (CIS homology domain; CH domain) are well conserved, while N-terminal region shares little similarity and varies in length. Most of them appear to be induced after stimulation with several different cytokines and at least three of them (CIS1, CIS3 and JAB) negatively regulate cytokine signal transduction by various means. Forced expression of CIS1 inhibits STAT5 activation by binding to cytokine receptors, whereas CIS3 and JAB directly binds to the kinase domain of JAKs, thereby inhibiting tyrosine kinase activity. Therefore, these CIS family members seem to function in a classical negative feedback loop of cytokine signaling. They may also be involved in suppression between cytokines frequently found in immune and inflammatory responses. JAB is found to inhibit interferon signaling, suggesting that elevated expression of JAB is involved in interferon-resistance. The mechanisms by which these inhibitors of cytokine signal transduction exert their effects and their physiological functions are crucial issues which need to be and will be addressed in the near future.
最近发现了一个细胞因子诱导的SH2蛋白（CIS）家族，其家族成员数量正在增加。在这个家族中，中央SH2结构域和C末端（约40个氨基酸）（CIS同源结构域；CH结构域）高度保守，而N末端区域相似度很低且长度各异。它们中的大多数似乎是在几种不同细胞因子刺激后被诱导产生的，并且其中至少有三个（CIS1、CIS3和JAB）通过各种方式对细胞因子信号转导进行负调控。CIS1的强制表达通过与细胞因子受体结合来抑制STAT5激活，而CIS3和JAB直接与JAKs的激酶结构域结合，从而抑制酪氨酸激酶活性。因此，这些CIS家族成员似乎在细胞因子信号传导的经典负反馈回路中发挥作用。它们也可能参与免疫和炎症反应中常见的细胞因子之间的抑制作用。发现JAB可抑制干扰素信号传导，这表明JAB表达升高与干扰素抵抗有关。这些细胞因子信号转导抑制剂发挥作用的机制及其生理功能是关键问题，在不久的将来需要并且将会得到解决。
