Ihle J N, Kerr I M
Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN 38105.
Trends Genet. 1995 Feb;11(2):69-74. doi: 10.1016/s0168-9525(00)89000-9.
Many cytokines mediate their biological effects through interaction with a distinct family of receptors termed the cytokine receptor superfamily. Although members of this family lack catalytic domains, they couple ligand binding to tyrosine phosphorylation. Recent studies have shown that a novel family of cytoplasmic protein tyrosine kinases, termed the Janus kinases (Jaks), associate with the cytokine receptors and are catalytically activated after ligand binding. The activated Jaks phosphorylate and activate members of a novel family of transcription factors termed signal transducers and activators of transcription (Stats). In addition, many cytokines induce the phosphorylation of SHC, Vav and the p85 subunit of PI-3 kinase. The region of the receptors proximal to the cytoplasmic membrane is required for Jak association, mitogenesis, Stat activation and Vav phosphorylation. The membrane-distal region, which contains the major sites of tyrosine phosphorylation, is required for phosphorylation of SHC and p85, not for mitogenesis, thus allowing functional dissection of the signaling pathways activated by cytokines.
许多细胞因子通过与一类独特的受体家族（称为细胞因子受体超家族）相互作用来介导其生物学效应。尽管该家族成员缺乏催化结构域，但它们将配体结合与酪氨酸磷酸化偶联起来。最近的研究表明，一类新的细胞质蛋白酪氨酸激酶家族，称为Janus激酶（Jaks），与细胞因子受体相关联，并在配体结合后被催化激活。活化的Jaks磷酸化并激活一类新的转录因子家族成员，称为信号转导子和转录激活子（Stats）。此外，许多细胞因子诱导SHC、Vav和PI-3激酶的p85亚基的磷酸化。靠近细胞质膜的受体区域是Jak结合、有丝分裂、Stat激活和Vav磷酸化所必需的。膜远端区域包含酪氨酸磷酸化的主要位点，是SHC和p85磷酸化所必需的，但不是有丝分裂所必需的，从而允许对细胞因子激活的信号通路进行功能剖析。
