鉴定heregulin,一个特定的激活器的p185erbB2的鉴定
W E Holmes1, M X Sliwkowski, R W Akita
1Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA 94080.
Science (New York, N.Y.)
|May 22, 1992
概括
研究人员确定了heregulin-alpha (HRG-alpha),一种特别诱导HER2 (人类表皮生长因子受体2) 氨酸激酶的酸化的蛋白质. HRG-alpha可能是HER2的天然配体,这是一种与癌症预后不佳相关的蛋白质.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 生物化学 生物化学
背景情况:
- 原型瘤基因HER2编码了一种跨膜氨酸激酶 (p185erbB2),这与各种人类癌症的不良预后有关.
- 过度表达p185erbB2是几种恶性瘤中重要的生物标志物.
研究的目的:
- 为了识别和描述p185erbB2氨酸激酶的自然连接体.
- 为了研究heregulin-alpha (HRG-alpha) 在p185erbB2信号传递中的作用.
主要方法:
- 从人类乳腺瘤细胞系净化HRG-alpha条件介质.
- 识别编码HRG家族成员的互补DNA克隆.
- 斯卡查德分析以确定重组HRG与表达p185erbB2的细胞的结合亲和力.
主要成果:
- HRG-α 特别诱导了p185erbB2.2. 的酸化.
- 确定了多个HRG变体,类似于表皮生长因子家族蛋白质.
- 证明了重组HRG与p185erbB2的高亲缘关系结合 (Kd = 105 +/- 15 pM).
- 在正常组织和癌症细胞系中检测到赫雷古林转录.
结论:
- 赫雷古林 (HRG) 是p185erbB2氨酸激酶的潜在天然连接体.
- 识别HRG可以了解癌症中的HER2信号通路.
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