MOLECULAR-CLONING AND EXPRESSION OF AN ADDITIONAL EPIDERMAL GROWTH-FACTOR RECEPTOR-RELATED GENE

被引:378
作者
PLOWMAN, GD
WHITNEY, GS
NEUBAUER, MG
GREEN, JM
MCDONALD, VL
TODARO, GJ
SHOYAB, M
机构
关键词
amphiregulin; ERBB2; ERBB3; receptor tyrosine kinase; sequence;
D O I
10.1073/pnas.87.13.4905
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Epidermal growth factor (EGF), transforming growth factor α (TGF-α), and amphiregulin are structurally and functionally related growth regulatory proteins. These secreted polypeptides all bind to the 170-kDa cell-surface EGF receptor, activating its intrinsic kinase activity. However, amphiregulin exhibits different activities than EGF and TGF-α in a number of biological assays. Amphiregulin only partially competes with EGF for binding EGF receptor, and amphiregulin does not induce anchorage-independent growth of normal rat kidney cells (NRK) in the presence of TGF-β. Amphiregulin also appears to abrogate the stimulatory effect of TGF-α on the growth of several aggressive epithelial carcinomas that overexpress EGF receptor. These findings suggest that amphiregulin may interact with a separate receptor in certain cell types. Here we report the cloning of another member of the human EGF receptor (HER) family of receptor tyrosine kinases, which we have named 'HER3/ERRB3'. The cDNA was isolated from a human carcinoma cell line, and its 6-kilobase transcript was identified in various human tissues. We have generated peptide-specific antisera that recognizes the 160-kDa HER3 protein when transiently expressed in COS cells. These reagents will allow us to determine whether HER3 binds amphiregulin or other growth regulatory proteins and what role HER3 protein plays in the regulation of cell growth.
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收藏
页码:4905 / 4909
页数:5
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