Zhuang H, Patel S V, He T C, Niu Z, Wojchowski D M
Department of Biochemistry & Molecular Biology and Veterinary Science, Pennsylvania State University, University Park 16802.
Biochem Biophys Res Commun. 1994 Oct 14;204(1):278-83. doi: 10.1006/bbrc.1994.2456.
Members of the Janus family of protein tyrosine kinases are emerging as primary, receptor-associated transducing factors among numerous cytokine systems. However, little is understood regarding mechanisms of recruitment of these kinases to receptor complexes and their ligand-dependent activation. To initially address these questions, we have assessed effects of ectopically expressing a carboxy-truncated form of Jak2 (Jak2-829) in Epo-responsive DAER cells. Expression of this truncation mutant at low levels efficiently inhibited both Epo-dependent activation of endogenous Jak2 and Epo-induced mitogenesis (10% to 39% of parental DAER cells). These results suggest that amino-terminal domains of Jak2 may mediate the assembly of Jak2/Epo receptor complexes and that integration of Jak2-829 into receptor complexes may effectively inhibit the activity of oligomeric Jak2/receptor assemblages.
蛋白酪氨酸激酶的Janus家族成员正成为众多细胞因子系统中主要的、与受体相关的转导因子。然而，对于这些激酶募集到受体复合物的机制及其配体依赖性激活，我们了解甚少。为了初步解决这些问题，我们评估了在促红细胞生成素（Epo）反应性DAER细胞中异位表达Jak2的羧基截短形式（Jak2-829）的影响。这种截短突变体的低水平表达有效地抑制了内源性Jak2的Epo依赖性激活以及Epo诱导的有丝分裂（为亲代DAER细胞的10%至39%）。这些结果表明，Jak2的氨基末端结构域可能介导Jak2/Epo受体复合物的组装，并且Jak2-829整合到受体复合物中可能有效地抑制寡聚Jak2/受体组合的活性。
