Cao H, Bangalore L, Dompé C, Bormann B J, Stern D F
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510.
J Biol Chem. 1992 Oct 5;267(28):20489-92.
The neu proto-oncogene encodes a receptor tyrosine kinase (p185) that is closely related to the epidermal growth factor receptor. It has been proposed that receptor tyrosine kinases are activated through oligomerization. Because this clustering model predicts that oligomerization of receptors is sufficient to activate them, we determined if p185 can be activated by introducing an extra cysteine proximal to the transmembrane domain. This should induce inter-receptor disulfide bonding and, according to the clustering model, activate the receptor. This amino acid substitution enhanced recovery of both normal and transforming neu proteins as dimers, with normal p185 recovered predominantly as monomers and transforming p185* as dimers. However, the cysteine substitution did not affect the transforming activity of the two proteins.
神经原癌基因编码一种受体酪氨酸激酶（p185），它与表皮生长因子受体密切相关。有人提出受体酪氨酸激酶通过寡聚化被激活。由于这种聚集模型预测受体的寡聚化足以激活它们，我们通过在跨膜结构域附近引入一个额外的半胱氨酸来确定p185是否可以被激活。这应该会诱导受体间二硫键的形成，并且根据聚集模型，激活受体。这种氨基酸取代增强了正常和转化型神经原蛋白作为二聚体的回收率，正常的p185主要以单体形式回收，而转化型p185*以二聚体形式回收。然而，半胱氨酸取代并不影响这两种蛋白的转化活性。
