Janus kinases in cytokine signalling
Janus kinases in cytokine signalling
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DOI：
10.1098/rstb.1996.0012
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发表时间：
1996-02-29
影响因子：
6.3
通讯作者：
Ihle, JN
中科院分区：
文献类型：
--
作者：
Ihle, JN
造血在很大程度上受细胞因子与细胞因子受体超家族受体结合的调节。尽管缺乏催化结构域，细胞因子受体超家族的成员介导酪氨酸磷酸化的配体依赖性激活，这对所有受体功能至关重要。最近的研究表明，这是通过Janus激酶（Jak）蛋白酪氨酸激酶家族成员的关联和激活介导的。激活的Jaks使受体磷酸化，为含有酪氨酸磷酸化的信号蛋白的SH2创造对接位点，这些蛋白与受体复合物结合后被酪氨酸磷酸化。酪氨酸磷酸化的底物包括转录蛋白家族的信号转导和激活因子（Stats）。各种细胞因子诱导酪氨酸磷酸化并激活六个家族成员中的一个或多个。Stat激活的模式提供了在其他信号通路的激活中未观察到的细胞因子个体水平。虽然不是有丝分裂反应所必需的，但据推测，Stats可能介导造血细胞的许多细胞因子特异性功能反应。
Hematopoiesis is largely regulated by the binding of cytokines to receptors of the cytokine receptor superfamily. Although lacking catalytic domains, members of the cytokine receptor superfamily mediate ligand dependent activation of tyrosine phosphorylation which is critical for all receptor functions. Recent studies have demonstrated that this is mediated through the association and activation of members of the Janus kinase (Jak) family of protein tyrosine kinases. The activated Jaks phosphorylate the receptors, creating docking sites for SH2 containing signalling proteins which are tyrosine phosphorylated following their association with the receptor complex. Among the substrates of tyrosine phosphorylation are members of the signal transducers and activators of transcription family of proteins (Stats). Various cytokines induce the tyrosine phosphorylation and activation of one or more of the six family members. The pattern of Stat activation provides a level of cytokine individuality that is not observed in the activation of other signalling pathways. Although not required for mitogenic responses, it is speculated that the Stats may mediate many of the cytokine specific functional responses of hematopoietic cells.