LIGAND-SPECIFIC ACTIVATION OF HER4/P180(ERBB4), A 4TH MEMBER OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR FAMILY
LIGAND-SPECIFIC ACTIVATION OF HER4/P180(ERBB4), A 4TH MEMBER OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR FAMILY
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DOI：
10.1073/pnas.90.5.1746
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发表时间：
1993-03-01
影响因子：
11.1
通讯作者：
SHOYAB, M
中科院分区：
文献类型：
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作者：
PLOWMAN, GD;CULOUSCOU, JM;SHOYAB, M
本报告描述了分离和重组表达的cDNA克隆编码HER 4，人表皮生长因子受体（EGFR）家族的第四个成员。HER 4/erbB 4基因编码180 kDa跨膜酪氨酸激酶（HER 4/p180 erbB 4），其胞外结构域与孤儿受体HER 3/p160 erbB 3最相似，而其胞质激酶结构域分别与EGFR和HER 2/p185 erbB 2具有79%和77%的同一性。HER 4最主要地在几种乳腺癌细胞系中以及在正常骨骼肌、心脏、垂体、脑和小脑中表达。此外，我们描述了肝素结合HER 4刺激因子从HepG 2细胞的部分纯化。发现该蛋白质特异性刺激HER 4/p180 erbB 4的内在酪氨酸激酶活性，而对EGFR、HER 2或HER 3的磷酸化没有直接影响。此外，这种肝素结合蛋白诱导过表达HER 4和HER 2的人乳腺肿瘤细胞系的表型分化和酪氨酸磷酸化。这些发现表明，这种配体-受体相互作用可能在一些正常和转化细胞的生长和分化中发挥作用。
This report describes the isolation and recombinant expression of a cDNA clone encoding HER4, the fourth member of the human epidermal growth factor receptor (EGFR) family. The HER4/erbB4 gene encodes a 180-kDa transmembrane tyrosine kinase (HER4/p180erbB4) whose extracellular domain is most similar to the orphan receptor HER3/p160erbB3, whereas its cytoplasmic kinase domain exhibits 79% and 77% identity with EGFR and HER2/p185erbB2, respectively. HER4 is most predominantly expressed in several breast carcinoma cell lines, and in normal skeletal muscle, heart, pituitary, brain, and cerebellum. In addition, we describe the partial purification of a heparin-binding HER4-stimulatory factor from HepG2 cells. This protein was found to specifically stimulate the intrinsic tyrosine kinase activity of HER4/p180erbB4 while having no direct effect on the phosphorylation of EGFR, HER2, or HER3. Furthermore, this heparin-binding protein induces phenotypic differentiation, and tyrosine phosphorylation, of a human mammary tumor cell line that overexpresses both HER4 and HER2. These findings suggest that this ligand-receptor interaction may play a role in the growth and differentiation of some normal and transformed cells.