Pim serine/threonine kinases regulate the stability of Socs-1 protein
Pim serine/threonine kinases regulate the stability of Socs-1 protein
复制标题
DOI：
10.1073/pnas.042035699
复制
发表时间：
2002-02-19
影响因子：
11.1
通讯作者：
Rothman, P
中科院分区：
文献类型：
--
作者：
Chen, XP;Losman, JA;Rothman, P
对SOCS-1缺陷小鼠的研究表明，SOCS-1参与了JAK-STAT（Janus酪氨酸激酶信号转导和转录激活因子）信号转导和T细胞发育的抑制。Socs-1蛋白的水平可能通过蛋白酶体途径调节。在这里，我们表明，Socs-1相互作用与胸腺细胞中的丝氨酸/苏氨酸激酶的Pim家族的成员。Pim激酶与Socs-1的共表达导致Socs-1蛋白的磷酸化和稳定化。与野生型小鼠相比，Pim-1（-/-）、Pim-2（-/-）小鼠中Socs-1的蛋白水平显著降低。与Socs-1（-/-）小鼠相似，Pim-1（-/-）、Pim-2（-/-）小鼠胸腺细胞在IL-4刺激后Stat 6磷酸化时间延长，提示Pim激酶可能通过调节Socs-1蛋白水平来调节腺嘌呤诱导的JAK-STAT信号转导。
Studies of SOCS-1-deficient mice have implicated Socs-1 in the suppression of JAK-STAT (Janus tyrosine kinase-signal transducers and activators of transcription) signaling and T cell development. It has been suggested that the levels of Socs-1 protein may be regulated through the proteasome pathway. Here we show that Socs-1 interacts with members of the Pim family of serine/threonine kinases in thymocytes. Coexpression of the Pim kinases with Socs-1 results in phosphorylation and stabilization of the Socs-1 protein. The protein levels of Socs-1 are significantly reduced in the Pim-1(-/-), Pim-2(-/-) mice as compared with wild-type mice. Similar to Socs-1(-/-) mice, thymocytes from Pim-1(-/-), Pim-2(-/-) mice showed prolonged Stat6 phosphorylation upon IL-4 stimulation, These data suggest that the Pim kinases may regulate cytokine-induced JAK-STAT signaling through modulation of Socs-1 protein levels.