Xia K, Mukhopadhyay N K, Inhorn R C, Barber D L, Rose P E, Lee R S, Narsimhan R P, D'Andrea A D, Griffin J D, Roberts T M
Dana-Farber Cancer Institute, Boston, MA, USA.
Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11681-6. doi: 10.1073/pnas.93.21.11681.
JAK2, a member of the Janus kinase superfamily was found to interact functionally with Raf-1, a central component of the ras/mitogen-activated protein kinase signal transduction pathway. Interferon-gamma and several other cytokines that are known to activate JAK2 kinase were also found to stimulate Raf-1 kinase activity toward MEK-1 in mammalian cells. In the baculovirus coexpression system, Raf-1 was activated by JAK2 in the presence of p21ras. Under these conditions, a ternary complex of p21ras, JAK2, and Raf-1 was observed. In contrast, in the absence of p21ras, coexpression of JAK2 and Raf-1 resulted in an overall decrease in the Raf-1 kinase activity. In addition, JAK2 phosphorylated Raf-1 at sites different from those phosphorylated by pp60v-src. In mammalian cells treated with either erythropoietin or interferon-gamma, a small fraction of Raf-1 coimmunoprecipitated with JAK2 in lysates of cells in which JAK2 was activated as judged by its state of tyrosine phosphorylation. Taken together, these data suggest that JAK2 and p21ras cooperate to activate Raf-1.
JAK2是Janus激酶超家族的成员，被发现与Raf-1在功能上相互作用，Raf-1是ras/丝裂原活化蛋白激酶信号转导途径的核心成分。已知能激活JAK2激酶的γ干扰素和其他几种细胞因子，也被发现能刺激哺乳动物细胞中Raf-1激酶对MEK-1的活性。在杆状病毒共表达系统中，在p21ras存在的情况下，Raf-1被JAK2激活。在这些条件下，观察到p21ras、JAK2和Raf-1的三元复合物。相反，在没有p21ras的情况下，JAK2和Raf-1的共表达导致Raf-1激酶活性总体下降。此外，JAK2在与pp60v-src磷酸化不同的位点使Raf-1磷酸化。在用促红细胞生成素或γ干扰素处理的哺乳动物细胞中，根据JAK2酪氨酸磷酸化状态判断其被激活的细胞裂解物中，一小部分Raf-1与JAK2共免疫沉淀。综上所述，这些数据表明JAK2和p21ras协同激活Raf-1。
