ERBB4 Membrane Protein Introduction

Introduction of ERBB4

ERBB4 is encoded by the ERBB4 gene which is located at 2q33.3-q34, and the gene mutations cause amyotrophic lateral sclerosis 19 (ALS19) which is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, leading to fatal paralysis. ERBB4 belongs to the ERBB family which includes Her1 (EGFR, ERBB1), Her2 (Neu, ERBB2), Her3 (ERBB3), and Her4 (ErbB4), ERBBs are structurally related to the epidermal growth factor receptor (EGFR). The molecular mass of ERBB4 is about 146 KDa.

Function of ERBB4 Membrane Protein

ERBB is a receptor tyrosine-protein kinase, the activity is regulated by Mg²⁺, lapatinib, gefitinib, etc. At the same time, it is also a single-pass type I membrane protein which spans the membrane once, with its N-terminus on the extracellular side of the membrane and removal of its signal sequence. Accordingly, ERBB4 plays a crucial role in cell migration, cell proliferation, central nervous system morphogenesis, heart development, and many other important biological processes. ERBB4 binds to and is active by neuregulins and EGF family members. What’ s more, it owns a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site, multiple furin-like cysteine-rich domains as well as a PDZ domain-binding motif. Once ERBB4 is activities in glioblastoma, it can contribute to increased tumorigenicity and influence therapeutic response, which makes ERBB4 a potential prognostic and therapeutic target. Besides, RBB4 signaling is associated with extracellular dopamine levels and can regulate spatial/working memory behaviors in dopaminergic axonal projections.

Fig .1 Structure of ERBB4 membrane protein

Application of ERBB4 Membrane Protein in Literature

1. Donoghue J.; et al. Activation of ERBB4 in glioblastoma can contribute to increased tumorigenicity and influence therapeutic response. Preprints. 2018, 2018060197.
   
   

   This article identifies elevated expression of the oncogenic ERBB4 variant JM-a-CYT-2 in glioblastoma and found p-ERBB4 to be an EGFR-independent prognostic marker for glioblastoma. Authors find an angiogenic role for ERBB4 in glioblastoma. ERBB4 is a rational therapeutic target in glioblastoma and have important implications for the design of trials targeting the EGFR pathway.

2. Skirzewski M., et al. ErbB4 signaling in dopaminergic axonal projections increases extracellular dopamine levels and regulates spatial/working memory behaviors. Mol Psychiatr. 2017. PubMed ID: 28727685
   
   

   This article reveals that direct NRG/ERBB4 signaling in DAergic axonal projections associated with dopamine (DA) homeostasis and that NRG/ERBB4 signaling in both dopamine neurons and GABAergic interneurons function in modulation of behaviors relevant to psychiatric disorders.

3. Knittle A.M., et al. Sumoylation regulates nuclear accumulation and signaling activity of the soluble intracellular domain of the erbb4 receptor tyrosine kinase. Journal of Biological Chemistry. 2017, 292(48). PubMed ID: 28974580
   
   

   This article reveals a SUMOylation-mediated mechanism which can regulate nuclear localization and function of the ICD of ERBB4 receptor tyrosine kinase. The SUMOylated ERBB4 ICD is tyrosine phosphorylated to a higher extent than the unmodified, and SUMOylation modulated the interaction of ERBB4 with the major nuclear export receptor for proteins.

4. Iwamoto R., et al. ERBB1 and ERBB4 generate opposing signals regulating mesenchymal cell proliferation during valvulogenesis. Journal of Cell Science. 2017, 130(7): 1321-1332. PubMed ID: 28232522
   
   

   This article focuses on the role of ERBB receptors in valvulogenesis in vivo. It suggests that opposing signals generated by different ERBB dimer combinations function in the same cardiac cushion mesenchymal cells for proper cardiac valve formation.

5. Streets A.J., et al. Parallel microarray profiling identifies ErbB4 as a determinant of cyst growth in ADPKD and a prognostic biomarker for disease progression. Am J Physiol Renal Physiol. 2017, 312(4): F577. PubMed ID: 28077374
   
   

   Authors in this article intend to identify new therapeutic targets and prognostic biomarkers of autosomal dominant polycystic kidney disease (ADPKD). They find that the EGF/ERBB family receptor ERBB4 is a major factor driving cyst growth in ADPKD. The date implicates ERBB4 activation as functionally relevant in ADPKD, both as a marker of disease activity and as a new therapeutic target in this major kidney disease.

ERBB4 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-ERBB4 antibody development services.

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