Ihle J N, Witthuhn B A, Quelle F W, Yamamoto K, Thierfelder W E, Kreider B, Silvennoinen O
Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN 38105.
Trends Biochem Sci. 1994 May;19(5):222-7. doi: 10.1016/0968-0004(94)90026-4.
A variety of cytokines, lymphokines and growth factors function by interacting with receptors that are members of the cytokine receptor superfamily. These receptors share extracellular motifs and have limited similarity in their cytoplasmic domains. Although lacking catalytic domains, this family of receptors couples ligand binding with the induction of tyrosine phosphorylation. Recent studies have shown that this is mediated by members of the Janus kinase (JAK) family of cytoplasmic protein tyrosine kinases. JAKs physically associate with the membrane-proximal region of the ligand-bound receptor, leading to their tyrosine phosphorylation and activation. The activated JAKs phosphorylate the receptors as well as cytoplasmic proteins belonging to a family of transcription factors called the signal transducers and activators of transcription (STATs), providing a novel signaling pathway that is shared by all members of the cytokine receptor superfamily.
多种细胞因子、淋巴因子和生长因子通过与作为细胞因子受体超家族成员的受体相互作用来发挥功能。这些受体具有共同的细胞外基序，并且其胞质结构域具有有限的相似性。尽管缺乏催化结构域，但该受体家族将配体结合与酪氨酸磷酸化的诱导偶联起来。最近的研究表明，这是由细胞质蛋白酪氨酸激酶的Janus激酶（JAK）家族成员介导的。JAK与配体结合的受体的膜近端区域发生物理缔合，导致其酪氨酸磷酸化并激活。活化的JAK使受体以及属于称为信号转导子和转录激活子（STAT）的转录因子家族的细胞质蛋白磷酸化，从而提供了细胞因子受体超家族所有成员共有的新型信号通路。
