人类GM-CSF受体生物学特性的研究

Biological Characterization of Human GMCSF Receptor

为了探讨人类ＧＭＣＳＦ受体（ＧＭＲ）的功能特性，将编码人ＧＭＲα和βｃ亚单位的ｃＤＮＡ转染到无ＧＭＲ表达的小鼠前Ｂ细胞系ＢａＦ３中。阳性转染子功能检测表明，表达ＧＭＲα的ＢａＦ３克隆能与配体低亲和力结合（Ｋｄ＝３．４ｎｍｏｌ／Ｌ），并仅在高浓度配体诱导后出现增殖反应；而共表达ＧＭ－Ｒα／β的ＢａＦ３克隆则能以高亲和力方式与配体结合（Ｋｄ＝９９ｐｍｏｌ／Ｌ），并表现出配体依赖性细胞增殖；增殖信号的传导与配体通过诱导βｃ磷酸化而活化胞浆Ｊａｋ２、Ｓｈｃ及Ｓｈｃ相关蛋白Ｐ１４５（ＳＨＩＰ）有关。提示这些信号分子可能在连结造血生长因子受体与细胞有丝分裂及其它反应的“激酶瀑布”中发挥着关键作用。

To investigate the characterization of human GMCSF receptor(GMR),mouse proB cell line BaF3 which does not express GMR was transfected with cDNAs encoding the and c subunit of the GMR.Functional expression of the positive transfectants was examined and BaF3 clone expressed hGMR alone could bind its ligand with low affinity (Kd=3.4nmol/L) and growth occurred only after stimulated by high concerntration of hGMCSF,whereas BaF3 clone coexpressed GMR / could bind GMCSF with high affinity (Kd=99 pmol/L)and have liganddependent proliferation.Signal transduction of proliferation was associated with activation of cytoplasmic Jak2,Shc and Shcassociated P145 (SHIP) proteins via phosphorylation of c.It is suggests that these signal molecules play a key role as part kinase cascadelinking hematopoietic growth factor receptors to mitogenesis and other cellular responses.