Wiegmann K, Schütze S, Kampen E, Himmler A, Machleidt T, Krönke M
Institut für Medizinische Mikrobiologie und Hygiene, Technische Universität München, Federal Republic of Germany.
J Biol Chem. 1992 Sep 5;267(25):17997-8001.
The numerous biological activities of tumor necrosis factor (TNF) appear mediated by two types of receptors of 55 kDa (TR55) and 75 kDa (TR75) molecular mass. To test TR55 for its individual role in signaling across the membrane, a cDNA coding for the human TR55 was stably expressed in murine 70Z/3 pre-B cells, which lack binding sites for, and proved nonresponsive to human TNF. The transfected TR55 showed high affinity ligand binding and active internalization. It is demonstrated that the TNF signaling cascade, i.e. stimulation of protein kinase C, sphingomyelinase, and phospholipase A2, production of the second messengers diacylglycerol and ceramide, can occur completely through exclusive binding of TNF to TR55. The p55 TNF-binding site functions as an autonomous TNF receptor that mediates key signal transduction pathways, which may control the majority of TNF actions.
肿瘤坏死因子(TNF)的众多生物学活性似乎是由两种分子量分别为55 kDa(TR55)和75 kDa(TR75)的受体介导的。为了测试TR55在跨膜信号传导中的个体作用,编码人TR55的cDNA在鼠70Z/3前B细胞中稳定表达,该细胞缺乏人TNF的结合位点且对人TNF无反应。转染的TR55表现出高亲和力配体结合和活跃的内化作用。结果表明,TNF信号级联反应,即蛋白激酶C、鞘磷脂酶和磷脂酶A2的刺激,第二信使二酰基甘油和神经酰胺的产生,完全可以通过TNF与TR55的特异性结合而发生。p55 TNF结合位点作为一个自主的TNF受体,介导关键的信号转导途径,这可能控制了大多数TNF的作用。