Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases

  title={Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases},
  author={Kermit L. Carraway and Janet L. Weber and Michelle J. Unger and Jessica Ledesma and Naichen Yu and Martin Gassmann and Cary Lai},
The neuregulins (NRGs) are a family of multipotent epidermal-growth-factor-like (EGF-like) factors that arise from splice variants of a single gene. They influence the growth, differentiation, survival and fate of several cell types. We have now discovered a set of new neuregulin-like growth factors, which we call neuregulin-2 (NRG-2): these are encoded by their own gene and exhibit a distinct expression pattern in adult brain and developing heart. Like NRG-1, the EGF-like domain of the new… 
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.
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.
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.
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.
Ligand Discrimination in Signaling through an ErbB4 Receptor Homodimer*
The results indicate that ErbB4 activation by growth factors is not generic and suggest that individual Erb B receptors can discriminate between different EGF-like ligands within the context of a single receptor dimer.
Neuregulin Growth Factors and Their ErbB Receptors Form a Potential Signaling Network for Schwannoma Tumorigenesis
It is reported that neoplastic Schwann cells within schwannomas overexpress multiple α and β transmembrane precursors from the class II and class III NRG-1 subfamilies, suggesting that autocrine, paracrine, and/or juxtacrine NRg-1/NRG-2 signaling promotesSchwannoma pathogenesis and that this signaling pathway may be an important therapeutic target in schwANNomas.
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.
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.
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 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.
The erbB3 gene product is a receptor for heregulin.
ErbB-3 and ErbB-4 function as the respective low and high affinity receptors of all Neu differentiation factor/heregulin isoforms.
Neu differentiation factor (NDF or heregulin) elevates tyrosine phosphorylation of the ErbB-2 receptor tyrosine kinase, and it was, therefore, thought to function as a ligand of this receptor.
Single-chain antibody-mediated intracellular retention of ErbB-2 impairs Neu differentiation factor and epidermal growth factor signaling.
The observations demonstrate that ErbB-2 plays a central role in the type I/EGFR-related family of receptors and that receptor transmodulation represents a crucial step in growth factor signaling.
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.
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.
Neuregulins and their receptors
Involvement of the neuregulins and their receptors in cardiac and neural development.
  • K. Carraway
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 1996
The observed defects, together with the localization of expression of the neuregulin signaling components within these tissues, highlight a paracrine mechanism for neurgulin-mediated intercellular communication.
ErbB‐2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer.
The results imply that ErbB‐2 is a pan‐ErbB subunit of the high affinity heterodimeric receptors for NDF and EGF, which may be due to its ability to potentiate in trans growth factor signaling.