Cao H, Bangalore L, Bormann B J, Stern D F
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510.
EMBO J. 1992 Mar;11(3):923-32. doi: 10.1002/j.1460-2075.1992.tb05131.x.
The neu proto-oncogene encodes a protein highly homologous to the epidermal growth factor receptor. The neu protein (p185) has a molecular weight of 185,000 Daltons and, like the EGF receptor, possesses tyrosine kinase activity. neu is activated in chemically induced rat neuro/glioblastomas by substitution of valine 664 with glutamic acid within the transmembrane domain. The activated neu* protein (p185*) has an elevated tyrosine kinase activity and a higher propensity to dimerize, but the mechanism of this activation is still unknown. We have used site-directed mutagenesis to explore the role of specific amino acids within the transmembrane domain in this activation. We found that the lateral position and rotational orientation of the glutamic acid in the transmembrane domain does not correlate with transformation. However, the primary structure in the vicinity of Glu664 plays a significant role in this activation. Our results suggest that the Glu664 activation involves highly specific interactions in the transmembrane domain of p185.
神经原癌基因编码一种与表皮生长因子受体高度同源的蛋白质。神经原蛋白（p185）分子量为185,000道尔顿，与表皮生长因子受体一样，具有酪氨酸激酶活性。在化学诱导的大鼠神经/胶质母细胞瘤中，通过跨膜结构域内缬氨酸664被谷氨酸替代，神经原被激活。激活的神经原蛋白（p185）具有升高的酪氨酸激酶活性和更高的二聚化倾向，但其激活机制仍不清楚。我们使用定点诱变来探究跨膜结构域内特定氨基酸在这种激活中的作用。我们发现跨膜结构域中谷氨酸的侧向位置和旋转方向与转化无关。然而，Glu664附近的一级结构在这种激活中起重要作用。我们的结果表明，Glu664激活涉及p185跨膜结构域中的高度特异性相互作用。
