Winkler M E, O'Connor L, Winget M, Fendly B
Department of Medicinal and Biomolecular Chemistry, Genentech Inc., South San Francisco, California.
Biochemistry. 1989 Jul 25;28(15):6373-8. doi: 10.1021/bi00441a033.
Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) compete with each other for binding to the EGF receptor. These two growth factors have similar actions, but there are distinguishable differences in their biological activities. It has never been clear how this one receptor can mediate different responses. A monoclonal antibody to the EGF receptor (13A9) has been identified which has only small effects on the binding of EGF to the EGF receptor, but which has very large effects on the binding of TGF alpha to the EGF receptor; 5 micrograms/mL antibody has been shown to totally block 0.87 microM TGF alpha from binding to purified EGF receptor and to lower both the high- and low-affinity binding constants of TGF alpha binding to EGF receptor on A431 cells by about 10-fold. The 13A9 antibody causes a 2.5-fold stimulation of the tyrosine kinase activity of partially purified EGF receptor, compared to a 4.0-fold stimulation of the tyrosine kinase activity by EGF under the same conditions. The data suggest either that the antibody stabilizes a conformation of the EGF receptor which is not favorable for TGF alpha binding or that it blocks a part of the surface of the receptor which is necessary for TGF alpha binding but not EGF binding.
表皮生长因子（EGF）和转化生长因子α（TGFα）相互竞争结合表皮生长因子受体。这两种生长因子具有相似的作用，但它们的生物学活性存在明显差异。一直不清楚这一种受体如何介导不同的反应。已鉴定出一种针对表皮生长因子受体的单克隆抗体（13A9），它对表皮生长因子与表皮生长因子受体的结合影响很小，但对转化生长因子α与表皮生长因子受体的结合影响很大；已证明5微克/毫升的该抗体能完全阻止0.87微摩尔的转化生长因子α与纯化的表皮生长因子受体结合，并使转化生长因子α与A431细胞上表皮生长因子受体的高亲和力和低亲和力结合常数均降低约10倍。与在相同条件下表皮生长因子对酪氨酸激酶活性的4.0倍刺激相比，13A9抗体使部分纯化的表皮生长因子受体的酪氨酸激酶活性有2.5倍的刺激。数据表明，要么该抗体稳定了表皮生长因子受体的一种不利于转化生长因子α结合的构象，要么它阻断了受体表面对于转化生长因子α结合但对表皮生长因子结合不必要的一部分。
