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Media type:
E-Article
Title:
Ligand-Specific Activation of HER4/p180erbB4, a Fourth Member of the Epidermal Growth Factor Receptor Family
Contributor:
Plowman, Gregory D.;
Culouscou, Jean-Michel;
Whitney, Gena S.;
Green, Janell M.;
Carlton, Gary W.;
Foy, Linda;
Neubauer, Michael G.;
Shoyab, Mohammed
imprint:
National Academy of Sciences of the United States of America, 1993
Published in:Proceedings of the National Academy of Sciences of the United States of America
Language:
English
ISSN:
0027-8424
Origination:
Footnote:
Description:
<p>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/p180<sup>erbB4</sup>) whose extracellular domain is most similar to the orphan receptor HER3/p160<sup>erbB3</sup>, whereas its cytoplasmic kinase domain exhibits 79% and 77% identity with EGFR and HER2/p185<sup>erbB2</sup>, 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/p180<sup>erbB4</sup>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.</p>