Huang L J, Constantinescu S N, Lodish H F
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
Mol Cell. 2001 Dec;8(6):1327-38. doi: 10.1016/s1097-2765(01)00401-4.
We show that Janus kinase 2 (JAK2), and more specifically just its intact N-terminal domain, binds to the erythropoietin receptor (EpoR) in the endoplasmic reticulum and promotes its cell surface expression. This interaction is specific as JAK1 has no effect. Residues 32 to 58 of the JAK2 JH7 domain are required for EpoR surface expression. Alanine scanning mutagenesis of the EpoR membrane proximal region reveals two modes of EpoR-JAK2 interaction. A continuous block of EpoR residues is required for functional, ligand-independent binding to JAK2 and cell surface receptor expression, whereas four specific residues are essential in switching on prebound JAK2 after ligand binding. Thus, in addition to its kinase activity required for cytokine receptor signaling, JAK is also an essential subunit required for surface expression of cytokine receptors.
我们发现，Janus激酶2（JAK2），更具体地说是其完整的N端结构域，在内质网中与促红细胞生成素受体（EpoR）结合，并促进其在细胞表面的表达。这种相互作用具有特异性，因为JAK1没有这种作用。JAK2 JH7结构域的32至58位残基是EpoR表面表达所必需的。对EpoR膜近端区域进行丙氨酸扫描诱变揭示了EpoR与JAK2相互作用的两种模式。EpoR残基的连续区域对于与JAK2的功能性、非配体依赖性结合以及细胞表面受体表达是必需的，而四个特定残基对于配体结合后激活预结合的JAK2至关重要。因此，除了细胞因子受体信号传导所需的激酶活性外，JAK也是细胞因子受体表面表达所需的必需亚基。
