DEMONSTRATION OF LIGAND-DEPENDENT SIGNALING BY THE ERBB-3 TYROSINE KINASE AND ITS CONSTITUTIVE ACTIVATION IN HUMAN BREAST-TUMOR CELLS

被引：128

作者：

KRAUS, MH ^{[1
]}

FEDI, P ^{[1
]}

STARKS, V ^{[1
]}

MURARO, R ^{[1
]}

AARONSON, SA ^{[1
]}

机构：

[1] UNIV ROMA LA SAPIENZA,DIPARTIMENTO MED SPERIMENTALE,I-00161 ROME,ITALY

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1993年 / 90卷 / 07期

关键词：

GP180(ERBB-3); RECEPTOR TYROSINE KINASE; TYROSINE PHOSPHORYLATION; MITOGENIC SIGNALING; NEOPLASIA;

D O I：

10.1073/pnas.90.7.2900

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 predicted human erbB-3 gene product is closely related to epidermal growth factor receptor (EGFR) and erbB-2, which have been implicated as oncogenes in model systems and human neoplasia. We expressed the erbB-3 coding sequence in NIH 3T3 fibroblasts and identified its product as a 180-kDa glycoprotein, gp180erbB-3. Tunicamycin and pulse-chase experiments revealed that the mature protein was processed by N-linked glycosylation of a 145-kDa erbB-3 core polypeptide. The intrinsic catalytic function of gp180erbB-3 was shown by its ability to autophosphorylate in vitro. Ligand-dependent signaling of its cytoplasmic domain was established employing transfectants that express a chimeric EGFR/erbB-3 protein, gp180EGFR/erbB-3. EGF induced tyrosine phosphorylation of the chimera and promoted soft agar colony formation of such transfectants. These findings combined with the detection of constitutive tyrosine phosphorylation of gp180erbB-3 in 4 of 12 human mammary tumor cell lines implicate the activated erbB-3 product in the pathogenesis of some human malignancies.

引用

页码：2900 / 2904

页数：5

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