IDENTIFICATION OF HEREGULIN, A SPECIFIC ACTIVATOR OF P185ERBB2

被引:994
作者
HOLMES, WE
SLIWKOWSKI, MX
AKITA, RW
HENZEL, WJ
LEE, J
PARK, JW
YANSURA, D
ABADI, N
RAAB, H
LEWIS, GD
SHEPARD, HM
KUANG, WJ
WOOD, WI
GOEDDEL, DV
VANDLEN, RL
机构
[1] GENENTECH INC,DEPT PROT CHEM,S SAN FRANCISCO,CA 94080
[2] GENENTECH INC,DEPT MOLEC BIOL,S SAN FRANCISCO,CA 94080
[3] GENENTECH INC,DEPT CELL BIOL,S SAN FRANCISCO,CA 94080
关键词
D O I
10.1126/science.256.5060.1205
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
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.
引用
收藏
页码:1205 / 1210
页数:6
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