Characterization of a growth factor that binds exclusively to the erbB-2 receptor and induces cellular responses

Ruth Lupu, Ramon Colomer, Bhanu Kannan, Marc E Lippman

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

The erbB-2 oncogene encodes a 185-kDa transmembrane protein that has been suggested to be a growth factor receptor. We have previously identified and purified a 30-kDa growth factor (gp30) that is a ligand for the p185erb-B-2 protein that at high concentrations induces growth inhibition of cells with erbB-2 amplification. We now report the purification and characterization of a protein from SKBr-3 human breast cancer cells with a molecular mass of 75 kDa (p75) that is a p185erbB-2 ligand. An affinity column coupled to the extracellular domain of p185erbB-2 was used for the purification. We found that p75 induced tyrosine phosphorylation of the erbB-2 oncoprotein, as determined by in vivo and in vitro phosphorylation and phosphoamino acid analysis. p75, as well as gp30, stimulated cell proliferation and colony formation of cells overexpressing erbB-2. The specificity of this effect was confirmed by showing that the antiproliferative effects of soluble erbB-2 extracellular domain were reversed by either p75 or gp30. p75 did not show binding to the epidermal growth factor receptor and had no growth effects on cells overexpressing epidermal growth factor receptor. These data show that SKBR-3 cells, which exhibit erbB-2 amplification and overexpression, secrete a growth factor that binds and activates p185erbB-2 specifically.

Original languageEnglish
Pages (from-to)2287-2291
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number6
StatePublished - Dec 1 1992
Externally publishedYes

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ErbB-2 Receptor
Intercellular Signaling Peptides and Proteins
Epidermal Growth Factor Receptor
Phosphorylation
Phosphoamino Acids
Ligands
Growth Factor Receptors
Oncogene Proteins
Growth
Oncogenes
Tyrosine
Cell Proliferation
Proteins

Keywords

  • Breast carcinomas
  • Growth factor
  • Oncogene

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Characterization of a growth factor that binds exclusively to the erbB-2 receptor and induces cellular responses. / Lupu, Ruth; Colomer, Ramon; Kannan, Bhanu; Lippman, Marc E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 6, 01.12.1992, p. 2287-2291.

Research output: Contribution to journalArticle

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