Identification of Heregulin, a Specific Activator of p185erbB2

@article{Holmes1992IdentificationOH,
  title={Identification of Heregulin, a Specific Activator of p185erbB2},
  author={William Evan Holmes and Mark X. Sliwkowski and Robert W. Akita and William J. Henzel and James M. Lee and John W. Park and Daniel G. Yansura and Nasrin Abadi and Helga Raab and Gail D. Lewis and H. Michael Shepard and W. J. Kuang and William l. Wood and David Norman Van Goeddel and Richard Vandlen},
  journal={Science},
  year={1992},
  volume={256},
  pages={1205 - 1210}
}
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-α (HRG-α) 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… 
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976 Citations

Role of heregulin in human cancer
  • M. Breuleux
  • Biology
    Cellular and Molecular Life Sciences
  • 2007
Abstract.Heregulin (HRG) is a soluble secreted growth factor, which, upon binding and activation of ErbB3 and ErbB4 transmembrane receptor tyrosine kinases, is involved in cell proliferation,…
Heregulin induces tyrosine phosphorylation of HER4/p180erbB4
TLDR
Findings suggest that activation of the HER4 receptor is involved in signal transduction by heregulin, a specific ligand for HER4 that fails to induce phosphorylation of HER2 in the absence of HER4.
HER4 Expression Correlates with Cytotoxicity Directed by a Heregulin-Toxin Fusion Protein (*)
TLDR
HAR-TX β2 was able to bind to and signal via tyrosine phosphorylation in cell lines that co-express HER2 and HER3 in the absence of HER4 without inducing cytotoxicity, suggesting it may prove to be a useful reagent for the targeting and elimination of Her4-positive tumor cells.
HER4 Receptor Activation and Phosphorylation of Shc Proteins by Recombinant Heregulin-Fc Fusion Proteins (*)
TLDR
After thrombin protease cleavage of rHRGs-T-Fc, their EGF-like domains were purified and shown to stimulate protein phosphorylation in HER4-expressing cells, suggesting a role for these adaptor molecules in HRG-mediated signaling.
The Transmembrane Heregulin Precursor Is Functionally Active*
TLDR
It is demonstrated that transmembrane heregulin is functionally active and suggested it is capable of playing a role in cell-cell communication and subsequent signal transduction in vivo.
Heregulins Implicated in Cellular Functions Other Than Receptor Activation
TLDR
Observations strongly support the notion that HRG1 splice variants have multifunctional properties, including previously unknown regulatory functions within the nucleus that are different from the activation of ErbB receptor signaling.
Recombinant heregulin-Pseudomonas exotoxin fusion proteins: interactions with the heregulin receptors and antitumor activity in vivo.
  • D. Yang, C. Kuan, M. Lippman
  • Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1998
TLDR
There is therapeutic potential of HRG-PE toxins in the therapy of cancers overexpressing the ErbB-4 or ErBB-2 plus Erb B-3 receptors, as well as other members of the type I receptor tyrosine kinase family.
Expression of messenger RNA for amphiregulin, heregulin, and cripto-1, three new members of the epidermal growth factor family, in human breast carcinomas
TLDR
There was no significant association between AR, HRG, and CR-1 expression and nodal status, EGF receptor, or c-erbB-2 protooncogene expression in these tumors, however, a significant associationBetween AR expression and estrogen receptor positivity was observed.
Roles for neuregulins in human cancer
TLDR
The analysis of ligand expression and/or activated receptors in tumor samples may broaden the group of patients that can benefit from targeted therapies.
A truncated intracellular HER2/neu receptor produced by alternative RNA processing affects growth of human carcinoma cells
TLDR
Alternative processing of the HER2 transcript is demonstrated and a potentially important growth regulatory role for intracellularly sequestered HER2 ECD in HER2-amplified human tumors is implicate.
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