Ligands for ErbB-family receptors encoded by a neuregulin-like gene

  title={Ligands for ErbB-family receptors encoded by a neuregulin-like gene},
  author={Han Soo Chang and David J. Riese and Walter Gilbert and David F. Stern and Uel Jackson McMahan},
Neuregulins (also called ARIA1, GGF2, heregulin3 or NDF4) are a group of polypeptide factors that arise from alternative RNA splicing of a single gene. Through their interaction with the ErbB family of receptors (ErbB2, ErbB3 and ErbB4), neuregulins help to regulate cell growth and differentiation in many tissues5–7. Here we report the cloning of a second neuregulin-like gene, neuregulin-2. The encoded product of the neuregulin-2 gene has a motif structure similar to that of neuregulins and an… 
Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4.
NRG3 is a novel, neural-enriched ligand for ErbB4, a novel protein that is structurally related to the neuregulins and shown to contain an extracellular domain with an epidermal growth factor (EGF) motif, a transmembrane domain, and a large cytoplasmic domain.
ErbB Tyrosine Kinases and the Two Neuregulin Families Constitute a Ligand-Receptor Network
It is concluded that the NRG-ErbB network represents a complex and nonredundant machinery developed for fine-tuning of signal transduction.
The Neuregulin Family of Genes and their Multiple Splice Variants in Breast Cancer
All four neuregulin genes are expressed and play an important role in mammary gland development and their presence may affect the efficacy of treatment with endocrine agents or with signal transduction inhibitors directed at the EGF receptor family members.
The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses.
The interactions found between receptor tyrosine kinases and MAGUKs at neuronal synapses may have important implications for activity-dependent plasticity.
Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase
The primary structure and the pattern of expression of NRG-4 suggest a physiological role distinct from that of the known ErbB ligands, as well as the strict specificity of this growth factor to ErbbB-4.
Neuregulins: functions, forms, and signaling strategies.
  • D. Falls
  • Biology
    Experimental cell research
  • 2003
The N-terminal Region of NTAK/Neuregulin-2 Isoforms Has an Inhibitory Activity on Angiogenesis*
Results suggest that the active site of NTAK is localized outside of the EGF-like domain but within the N-terminal region, including the Ig-likedomain, of NtaK.
A Novel Juxtamembrane Domain Isoform of HER4/ErbB4
Novel alternatively spliced isoforms of HER4 exist, they are distributed differentially in vivo in mouse and human tissues, that they are both activated by HER4 ligands, and that they may represent cleavable and noncleavable forms of Her4.
Differential Signaling by the Epidermal Growth Factor-like Growth Factors Neuregulin-1 and Neuregulin-2*
The neuregulins comprise a subfamily of epidermal growth factor (EGF)-like growth factors that elicit diverse cellular responses by activating members of the ErbB family of receptor tyrosine kinases and results imply that EGF-like ligands might elicit differential signaling within the context of a single receptor heterodimer.


Multiple essential functions of neuregulin in development
It is shown that neUREgulin -/ - embryos die during embryogenesis and display heart malformations, and the phenotype demonstrates that in vivo neuregulin acts locally and frequently in a paracrine manner.
The cellular response to neuregulins is governed by complex interactions of the erbB receptor family
The results provide the first comprehensive analysis of the response of this receptor family to a single peptide agonist and demonstrate the existence of several previously undocumented receptor interactions driven by neuregulin.
Requirement for neuregulin receptor erbB2 in neural and cardiac development
The results demonstrate the importance of erbB2 in neural and cardiac development and find that mutant embryos die before Ell, probably as a result of dysfunctions associated with a lack of cardiac trabeculae.
Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family.
The findings suggest that this ligand-receptor interaction may play a role in the growth and differentiation of some normal and transformed cells.
Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin.
The heregulin/neu differentiation factor gene products were purified and cloned based on their ability to stimulate the phosphorylation of a 185-kDa protein in human breast carcinoma cell lines known to express erbB2, indicating that other components besides erBB2 may be required forHeregulin binding.
Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor
It is demonstrated that ErbB4 is an essential in vivo regulator of both cardiac muscle differentiation and axon guidance in the central nervous system (CNS) and differences in the hindbrain phenotypes of these mutants are consistent with the action of a new Erb B4 ligand in the CNS.
Heregulin induces tyrosine phosphorylation of HER4/p180erbB4
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.
Neuregulins and their receptors