EGF Membrane Protein Introduction

Introduction of EGF

EGF is encoded by the EGF gene and is also known as Pro-epidermal growth factor. It belongs to the EGF family of growth factors, which consists of about 11 members. These factors have a short cytoplasmic tail, a transmembrane domain, and an ectodomain with a single 40-45 amino acid motif (6 kDa) known as the EGF-like domain. The pre-EGF is the largest in the EGF family and is about 170 kDa in weight. After being inserted into the plasma membrane, the 170 kDa precursor is cleaved to release the ectodomain of 150 kDa known as pro-EGF. Furthermore, the 6 kDa EGF can be released from the pro-EGF by proteolysis.

Function of EGF Membrane Protein

EGF is synthesized in the kidney, and EGF receptors are present in mesangial, tubular, and interstitial cells. EGF stimulates in vitro tubular cell proliferation and influences the synthesis and turnover of ECM proteins. EGF plays an important role in the development, maturation, and maintenance of gut homeostasis because EGF enhances Na⁺ absorption in the gastrointestinal tract. In isolated rat enterocytes, administrating EGF (200 ng/ml) stimulates Na⁺/H⁺ exchange activity by 1.8-fold. Additionally, EGF is important in the prevention and treatment of inflammatory conditions. EGFs and their receptors are widespread in many tissues and participate in specific developmental processes, such as neonatal eyelid opening and tooth eruption. It is also believed to play an important role in the pathogenesis of necrotizing enterocolitis because the decreased levels of EGF have been demonstrated in the saliva and serum of premature infants with Necrotizing enterocolitis. EGF is involved in the regulation of many physiological signaling pathways, and its dysregulation can cause kidney disease, heart disease, and cancer.

Fig.1 EGF and its receptor survival signaling pathways (Miyamoto, 2017).

Application of EGF Membrane Protein in Literature

1. Chen R., et al. The soluble protease ADAMDEC1 released from activated platelets hydrolyzes platelet membrane pro-epidermal growth factor (EGF) to active high-molecular-weight EGF. The Journal of Biological Chemistry. 2017, 292(24):10112-10122. PubMed ID: 28455445
   
   

   This article concludes that activated platelets release ADAMDEC1, which hydrolyzes pro-EGF to soluble HMW-EGF.

2. Thomas J.T., et al. SMOC Binds to Pro-EGF, but Does Not Induce Erk Phosphorylation via the EGFR. PLoS ONE. 2016, 11(4):e0154294. PubMed ID: 27101391
   
   

   The results of this article suggest that the interaction of SMOC/pro-EGF does not require the C-terminal extracellular calcium-binding (EC) domain of SMOC or the EGF domain of pro-EGF.

3. Groenestege W.M.T., et al. Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J. Clin. Invest. 2007, 117(8):2260-2267. PubMed ID: 17671655
   
   

   Authors in this article perform RT-PCR on various human tissues to study the tissue distribution of pro-EGF and EGFR. For pro-EGF, PCR amplification products were detected in, e.g., kidney, salivary gland, cerebrum, and prostate, whereas no expression was detected in the adrenal gland, liver, cerebellum, and placenta. The EGFR showed a ubiquitous expression pattern since all tissues tested were positive by RT-PCR analysis.

4. Miyamoto Y., et al. Recent Advances in Targeting the EGFR Signaling Pathway for the Treatment of Metastatic Colorectal Cancer. International Journal of Molecular Sciences. 2017, 18(4):752. PubMed ID: 28368335
   
   

   This article reports the outcomes for metastatic colorectal cancer (mCRC) patients have been improved by treatment with anti-epidermal growth factor receptor (anti-EGFR) antibodies, particularly when combined with predictive biomarkers to select patients lacking RAS mutations.

5. Mitsuishi Y., et al. Epidermal growth factor receptor/extracellular signal-regulated kinase pathway enhances mineralocorticoid receptor transcriptional activity through protein stabilization. Mol. Cell. Endocrinol. 2018, 473:89-99. PubMed ID: 29391190
   
   

   This article suggests that EGFR/ERK pathway activation is considered as one of the underlying mechanisms of aberrant MR activation and EGFR/ERK pathway blockade could be an alternative approach for the prevention of MR-related cardiovascular events.

EGF Preparation Options

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Reference

1. Miyamoto Y., et al. (2017) Recent Advances in Targeting the EGFR Signaling Pathway for the Treatment of Metastatic Colorectal Cancer. International Journal of Molecular Sciences. 18(4).

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