Science. 1992 May 22;256(5060):1205-10.

Identification of heregulin, a specific activator of p185erbB2.

Holmes WE, Sliwkowski MX, Akita RW, Henzel WJ, Lee J, Park JW, Yansura D, Abadi N, Raab H, Lewis GD, et al.

Source

Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA 94080.

Abstract

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 (Kd) = 105 +/- 15 picomolar]. Heregulin transcripts were identified in several normal tissues and cancer cell lines. The HRGs may represent the natural ligands for p185erbB2.

PMID:: 1350381; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances, Secondary Source ID

Publication Types

Comparative Study

MeSH Terms

Substances

Secondary Source ID

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

ERBB2 Gene - Genetics Home Reference

Research Materials

anti-Neuregulin 1 (NRG1) antibody - antibodies-online

Supplemental Content

Save items

Related citations in PubMed

Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2. [Science. 1990]
Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2.
Lupu R, Colomer R, Zugmaier G, Sarup J, Shepard M, Slamon D, Lippman ME. Science. 1990 Sep 28; 249(4976):1552-5.
Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. [J Biol Chem. 1994]
Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin.
Sliwkowski MX, Schaefer G, Akita RW, Lofgren JA, Fitzpatrick VD, Nuijens A, Fendly BM, Cerione RA, Vandlen RL, Carraway KL 3rd. J Biol Chem. 1994 May 20; 269(20):14661-5.
An oncogenic point mutation confers high affinity ligand binding to the neu receptor. Implications for the generation of site heterogeneity. [J Biol Chem. 1992]
An oncogenic point mutation confers high affinity ligand binding to the neu receptor. Implications for the generation of site heterogeneity.
Ben-Levy R, Peles E, Goldman-Michael R, Yarden Y. J Biol Chem. 1992 Aug 25; 267(24):17304-13.
Review Neu and its ligands: from an oncogene to neural factors. [Bioessays. 1993]
Review Neu and its ligands: from an oncogene to neural factors.
Peles E, Yarden Y. Bioessays. 1993 Dec; 15(12):815-24.
Review The epidermal growth factor receptor and its ligands. [Cancer Treat Res. 1989]
Review The epidermal growth factor receptor and its ligands.
Wells A. Cancer Treat Res. 1989; 47:143-68.

See reviews... See all...

Cited by over 100 PubMed Central articles

High heregulin expression is associated with activated HER3 and may define an actionable biomarker in patients with squamous cell carcinomas of the head and neck. [PLoS One. 2013]
High heregulin expression is associated with activated HER3 and may define an actionable biomarker in patients with squamous cell carcinomas of the head and neck.
Shames DS, Carbon J, Walter K, Jubb AM, Kozlowski C, Januario T, AnDo, Fu L, Xiao Y, Raja R, et al. PLoS One. 2013; 8(2):e56765. Epub 2013 Feb 28.
ErbB2 dephosphorylation and anti-proliferative effects of neuregulin-1 in ErbB2-overexpressing cells; re-evaluation of their low-affinity interaction. [Sci Rep. 2013]
ErbB2 dephosphorylation and anti-proliferative effects of neuregulin-1 in ErbB2-overexpressing cells; re-evaluation of their low-affinity interaction.
Wang R, Iwakura Y, Araki K, Keino-Masu K, Masu M, Wang XY, Takei N, Higashiyama S, Nawa H. Sci Rep. 2013; 3:1402.
ErbB1-4-dependent EGF/neuregulin signals and their cross talk in the central nervous system: pathological implications in schizophrenia and Parkinson's disease. [Front Cell Neurosci. 2013]
ErbB1-4-dependent EGF/neuregulin signals and their cross talk in the central nervous system: pathological implications in schizophrenia and Parkinson's disease.
Iwakura Y, Nawa H. Front Cell Neurosci. 2013; 7:4. Epub 2013 Feb 13.

See all...

Structures reported by this article

Heregulin-Alpha Epidermal Growth Factor-Like Domain, Nmr, Minimized Average Structure

PDB: 1HAF

Source: Homo sapiens

Method: Solution Nmr

See all 2 structures...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
BioSystems
Pathways and biological systems (BioSystems) that cite the current articles. Citations are from the BioSystems source databases (KEGG and BioCyc).
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Gene
Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
Gene (OMIM)
Gene records associated with Online Mendelian Inheritance in Man (OMIM) records that cite the current articles in their reference lists.
HomoloGene
HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
Nucleotide
Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
Nucleotide (RefSeq)
NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
OMIM (calculated)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as references in the light bulb links within or in the citations at the end of the OMIM record. The references available through the light bulb link are collected using the PubMed related articles algorithm to identify records with similar terminology to the OMIM record.
OMIM (cited)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as reference cited at the end of the OMIM record.
Protein (RefSeq)
NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
Protein Clusters
Clusters of related proteins from the Protein Clusters database that cite the current articles. Sources of references in Protein Clusters include the associated Gene and Conserved Domain records as well as NCBI added citations.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Taxonomy via GenBank
Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
UniGene
UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
Domains
Conserved Domain Database (CDD) records that cite the current articles. Citations are from the CDD source database records (PFAM, SMART).
Protein
Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
Structure
Three-dimensional structure records in the NCBI Structure database for data reported in the current articles.
GEO Profiles
Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.
Cited in Books
NCBI Bookshelf books that cite the current articles.

Recent activity

Clear Turn Off Turn On

Identification of heregulin, a specific activator of p185erbB2.
Identification of heregulin, a specific activator of p185erbB2.
Science. 1992 May 22 ;256(5060):1205-10.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: