Hellgren G, Albertsson-Wikland K, Billig H, Carlsson L M, Carlsson B
Research Centre for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
J Interferon Cytokine Res. 2001 Feb;21(2):75-83. doi: 10.1089/107999001750069935.
Janus kinases (Jak) play an important role in the initial steps of cytokine receptor signaling. The specificity of the four members of the Jak family (Jak1, Jak2, Jak3, and Tyk2) for different cytokine receptors is not fully understood. Recent studies have indicated that a specific cytokine receptor can activate several Jak and that this may differ between tissues. The growth hormone receptor (GHR) is believed to interact predominantly with Jak2, but studies on cell lines have shown that it may also induce phosphorylation of Jak1 and Jak3. Little is known about the interaction between the GHR and Jak in tissues. Our aim, therefore, was to elucidate which Jak interact with the GHR in two target tissues for GH, liver and adipose tissue. Western blot analysis showed that all four members of the Jak family are present in both rat liver and adipose tissue. However, coprecipitation using an anti-GHR antibody revealed that only Jak1 and Jak2 were associated with the GHR in these tissues. The relative amount of Jak1 and Jak2 that coprecipitated with the GHR differed markedly between tissues. In the liver, Jak2 dominated, and only a small amount of Jak1 was detected. In adipose tissue, at least one third of the coprecipitated Jak was Jak1. This is the first study to show that both Jak1 and Jak2 are associated with the GHR in rat tissues. The difference in the ratio between GHR-associated Jak1 and Jak2 in liver and adipose tissue may indicate that GHR signaling in different tissues could differ in terms of Jak specificity.
Janus激酶（Jak）在细胞因子受体信号传导的起始步骤中发挥重要作用。Jak家族的四个成员（Jak1、Jak2、Jak3和Tyk2）对不同细胞因子受体的特异性尚未完全明确。最近的研究表明，一种特定的细胞因子受体可以激活多种Jak，并且这在不同组织之间可能存在差异。生长激素受体（GHR）被认为主要与Jak2相互作用，但对细胞系的研究表明，它也可能诱导Jak1和Jak3的磷酸化。关于GHR与Jak在组织中的相互作用知之甚少。因此，我们的目的是阐明在生长激素的两个靶组织肝脏和脂肪组织中，哪些Jak与GHR相互作用。蛋白质免疫印迹分析表明，Jak家族的所有四个成员在大鼠肝脏和脂肪组织中均有表达。然而，使用抗GHR抗体进行的共沉淀显示，在这些组织中只有Jak1和Jak2与GHR相关联。与GHR共沉淀的Jak1和Jak2的相对量在不同组织之间存在显著差异。在肝脏中，Jak2占主导地位，仅检测到少量的Jak1。在脂肪组织中，共沉淀的Jak中至少三分之一是Jak1。这是第一项表明Jak1和Jak2在大鼠组织中均与GHR相关联的研究。肝脏和脂肪组织中与GHR相关的Jak1和Jak2比例的差异可能表明，不同组织中的GHR信号传导在Jak特异性方面可能存在差异。
