JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor α and βc subunit, respectively, and are activated upon IL-5 stimulation
JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor α and βc subunit, respectively, and are activated upon IL-5 stimulation
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DOI：
10.1182/blood.v91.7.2264.2264_2264_2271
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发表时间：
1998-04-01
期刊：
影响因子：
20.3
通讯作者：
Takatsu, K
中科院分区：
文献类型：
--
作者：
Ogata, N;Kouro, T;Takatsu, K
人类白细胞介素-5受体（hIL-5R）由一个独特的亚基（hIL-5R α）和一个共同的β亚基（β c）组成，可激活两种Janus激酶（JAK1和JAK2）和一个信号转换器和转录激活因子（STAT5）。我们使用抗il - 5r α和抗β - c单克隆抗体，通过免疫沉淀分析了il - 5r α和β - c之间的相互作用。在hil -5应答细胞系TF-h5R α中也评估了JAK1和JAK2与每个hIL-5R亚基的结合。我们观察到，IL-5刺激诱导β c向il - 5r α募集，尽管在没有IL-5的情况下，亚单位保持独立。在没有IL-5的情况下，JAK2和JAK1分别与hIL-5R α和β c相关，IL-5刺激导致JAK2、JAK1、β c和STAT5的酪氨酸磷酸化，而且即使在没有JAK1激活的情况下，IL-5诱导的IL-5R亚基的二聚化也会引起JAK2的激活和β c的磷酸化，而且JAK1的酪氨酸磷酸化依赖于JAK2的激活。对hIL-5R α c端截断的细胞质结构域的详细研究表明，346-387位置的细胞质拉伸包含富含脯氨酸的区域，是JAK2结合所必需的，这些观察结果表明，hIL-5R α相关JAK2的激活对于IL-5信号事件是必不可少的。(C) 1998年由美国血液病学会出版。
The human interleukin-5 receptor (hIL-5R) consists of a unique of subunit (hIL-5R alpha) and a common beta subunit (beta c) that activate two Janus kinases (JAK1 and JAK2) and a signal transducer and activator of transcription (STAT5), The precise stoichiometry of the hIL-5R subunits and the role of JAK kinases used in IL-5 signaling were investigated, We analyzed the interaction between hIL-5R alpha and beta c by immunoprecipitation using anti-hIL-5R alpha and anti-beta c monoclonal antibodies. The binding of JAK1 and JAK2 to each hIL-5R subunit was also evaluated in the hIL-5-responsive cell line, TF-h5R alpha. It was observed that IL-5 stimulation induced the recruitment of beta c to hIL-5R alpha, although in the absence of IL-5 the subunits remain independent. In the absence of IL-5, JAK2 and JAK1 were associated with hIL-5R alpha and beta c, respectively, IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1, beta c, and STAT5, Moreover, IL-5-induced dimerization of IL-5R subunits caused JAK2 activation and beta c phosphorylation even in the absence of JAK1 activation, Furthermore, tyrosine phosphorylation of JAK1 was dependent on the activation of JAK2, Detailed study of the C-terminal truncated cytoplasmic domain of hIL-5R alpha revealed that the cytoplasmic stretch at position 346-387, containing the proline-rich region, is necessary for JAK2 binding, These observations suggest that activation of hIL-5R alpha-associated JAK2 is indispensable for the IL-5 signaling event. (C) 1998 by The American Society of Hematology.