IDENTIFICATION OF HEREGULIN, A SPECIFIC ACTIVATOR OF P185ERBB2
IDENTIFICATION OF HEREGULIN, A SPECIFIC ACTIVATOR OF P185ERBB2
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DOI：
10.1126/science.256.5060.1205
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发表时间：
1992-05-22
期刊：
影响因子：
56.9
通讯作者：
VANDLEN, RL
中科院分区：
文献类型：
--
作者：
HOLMES, WE;SLIWKOWSKI, MX;VANDLEN, RL
原癌基因命名为erbB 2或HER 2编码一个185千道尔顿的跨膜酪氨酸激酶（p185 erbB 2），其过表达与几种人类恶性肿瘤的预后不良相关。从人乳腺癌细胞系的条件培养基中纯化了一种特异性诱导p185 erbB 2磷酸化的45千道尔顿蛋白调蛋白-α（HRG-α）。几个互补的DNA克隆编码相关的HRGs被确定，所有这些都是类似的蛋白质在表皮生长因子家族。重组HRG与表达p185 erbB 2的乳腺肿瘤细胞系结合的Scatchard分析显示了单一的高亲和力结合位点[解离常数（K（d））= 105 +/- 15皮摩尔]。在几种正常组织和癌细胞系中鉴定了调蛋白转录物。HRG可能代表p185 erbB 2的天然配体。
The proto-oncogene designated erbB2 or HER2 encodes a 185-kilodalton transmembrane tyrosine kinase (p185erbB2), whose overexpression has been correlated with a poor prognosis in several human malignancies. A 45-kilodalton protein heregulin-alpha (HRG-alpha) that specifically induced phosphorylation of p185erbB2 Was purified from the conditioned medium of a human breast tumor cell line. Several complementary DNA clones encoding related HRGs were identified, all of which are similar to proteins in the epidermal growth factor family. Scatchard analysis of the binding of recombinant HRG to a breast tumor cell line expressing p185erbB2 showed a single high affinity binding site [dissociation constant (K(d)) = 105 +/- 15 picomolar]. Heregulin transcripts were identified in several normal tissues and cancer cell lines. The HRGs may represent the natural ligands for p185erbB2.