Epidermal growth factor

Last updated

EGF
1a3p egf.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases EGF , HOMG4, URG, epidermal growth factor, epithelial growth factor
External IDs OMIM: 131530; MGI: 95290; HomoloGene: 1483; GeneCards: EGF; OMA:EGF - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1950

13645

Ensembl

ENSG00000138798

ENSMUSG00000028017

UniProt

P01133

P01132

RefSeq (mRNA)

NM_001178130
NM_001178131
NM_001963
NM_001357021

NM_010113
NM_001310737
NM_001329594

RefSeq (protein)

NP_001171601
NP_001171602
NP_001954
NP_001343950

NP_001297666
NP_001316523
NP_034243

Location (UCSC) Chr 4: 109.91 – 110.01 Mb Chr 3: 129.47 – 129.55 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-kDa [5] and has 53 amino acid residues and three intramolecular disulfide bonds. [6]

Contents

EGF was originally described as a secreted peptide found in the submaxillary glands of mice and in human urine. EGF has since been found in many human tissues, including platelets, [7] submandibular gland (submaxillary gland), [8] and parotid gland. [8] Initially, human EGF was known as urogastrone. [9]

Structure

In humans, EGF has 53 amino acids (sequence NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCzYRDLKWWELR), [6] with a molecular mass of around 6 kDa. [5] It contains three disulfide bridges (Cys6-Cys20, Cys14-Cys31, Cys33-Cys42). [6]

Function

EGF, via binding to its cognate receptor, results in cellular proliferation, differentiation, and survival. [10]

Salivary EGF, which seems to be regulated by dietary inorganic iodine, also plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. The biological effects of salivary EGF include healing of oral and gastroesophageal ulcers, inhibition of gastric acid secretion, stimulation of DNA synthesis as well as mucosal protection from intraluminal injurious factors such as gastric acid, bile acids, pepsin, and trypsin and to physical, chemical and bacterial agents. [8]

Biological sources

The Epidermal growth factor can be found in platelets, [7] urine, saliva, milk, tears, and blood plasma. [11] It can also be found in the submandibular glands, [8] [12] and the parotid gland. [8] [12] The production of EGF has been found to be stimulated by testosterone.[ citation needed ]

Polypeptide growth factors

Polypeptide growth factors include: [13]

Sr.NoGrowth factorSourceMajor function
1Epidermal growth factor (EGF)Salivary glandStimulates growth of epidermal and epithelial cells
2 Platelet derived growth factor PlateletsStimulates growth of mesenchymal cells, promotes wound healing
3 Transforming growth factor-alpha (TGF-α)Epithelial cellSimilar to EGF
4 Transforming growth factor-beta (TGF-β)Platelets, Kidney, PlacentaInhibitory effect on cultures tumor cell
5 Erythropoietin KidneyStimulates development of erythropoietic cells
6 Nerve growth factor (NGF)Salivary glandStimulates the growth of sensory nerves
7 Insulin-like growth factor SerumStimulates incorporation of sulfates into cartilage, exerts insulin-like action on certain cells
8 Tumor necrosis factor MonocytesNecrosis of tumor cells
9 Interleukin-1 Monocytes, LeukocytesStimulates synthesis of IL-2
10 Interleukin-2 LymphocytesStimulates growth and maturation of T-cells

Mechanism

Diagram showing key components of the MAPK/ERK pathway. In the diagram, "P" represents phosphate. Note EGF at the very top. MAPKpathway diagram.svg
Diagram showing key components of the MAPK/ERK pathway. In the diagram, "P" represents phosphate. Note EGF at the very top.

EGF acts by binding with high affinity to epidermal growth factor receptor (EGFR) on the cell surface. This stimulates ligand-induced dimerization, [14] activating the intrinsic protein-tyrosine kinase activity of the receptor (see the second diagram). The tyrosine kinase activity, in turn, initiates a signal transduction cascade that results in a variety of biochemical changes within the cell – a rise in intracellular calcium levels, increased glycolysis and protein synthesis, and increases in the expression of certain genes including the gene for EGFR – that ultimately lead to DNA synthesis and cell proliferation. [15]

EGF-family / EGF-like domain

EGF is the founding member of the EGF-family of proteins. Members of this protein family have highly similar structural and functional characteristics. Besides EGF itself other family members include: [16]

All family members contain one or more repeats of the conserved amino acid sequence:

CX7CX4-5CX10-13CXCX8GXRC

Where C is cysteine, G is glycine, R is arginine, and X represents any amino acid. [16]

This sequence contains six cysteine residues that form three intramolecular disulfide bonds. Disulfide bond formation generates three structural loops that are essential for high-affinity binding between members of the EGF-family and their cell-surface receptors. [5]

Interactions

Epidermal growth factor has been shown to interact with epidermal growth factor receptors. [17] [18]

Medical uses

Recombinant human epidermal growth factor, sold under the brand name Heberprot-P, is used to treat diabetic foot ulcers. It can be given by injection into the wound site, [19] or may be used topically. [20] Tentative evidence shows improved wound healing. [21] Safety has been poorly studied. [21]

EGF is used to modify synthetic scaffolds for manufacturing of bioengineered grafts by emulsion electrospinning or surface modification methods. [22] [23]

Bone regeneration

EGF plays an enhancer role on the osteogenic differentiation of dental pulp stem cells (DPSCs) because it is capable of increasing extracellular matrix mineralization. A low concentration of EGF (10 ng/ml) is sufficient to induce morphological and phenotypic changes. These data suggests that DPSCs in combination with EGF could be an effective stem cell-based therapy to bone tissue engineering applications in periodontics and oral implantology. [24]

History

EGF was the second growth factor to be identified. [25] Initially, human EGF was known as urogastrone. [9] Stanley Cohen discovered EGF while working with Rita Levi-Montalcini at the Washington University in St. Louis during experiments researching nerve growth factor. For these discoveries Levi-Montalcini and Cohen were awarded the 1986 Nobel Prize in Physiology or Medicine.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000138798 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028017 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 Harris RC, Chung E, Coffey RJ (March 2003). "EGF receptor ligands". Experimental Cell Research. 284 (1): 2–13. doi:10.1016/S0014-4827(02)00105-2. PMID   12648462.
  6. 1 2 3 Carpenter G, Cohen S (May 1990). "Epidermal growth factor". The Journal of Biological Chemistry. 265 (14): 7709–12. doi: 10.1016/S0021-9258(19)38983-5 . PMID   2186024.
  7. 1 2 Custo S, Baron B, Felice A, Seria E (5 July 2022). "A comparative profile of total protein and six angiogenically-active growth factors in three platelet products". GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW. 11 (Doc06): Doc06. doi:10.3205/iprs000167. PMC   9284722 . PMID   35909816.
  8. 1 2 3 4 5 Venturi S, Venturi M (2009). "Iodine in evolution of salivary glands and in oral health". Nutrition and Health. 20 (2): 119–34. doi:10.1177/026010600902000204. PMID   19835108. S2CID   25710052.
  9. 1 2 Hollenberg MD, Gregory H (May 1980). "Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives" . Molecular Pharmacology. 17 (3): 314–320. doi:10.1016/S0026-895X(25)14104-7. PMID   6248761.
  10. ↑ Herbst RS (2004). "Review of epidermal growth factor receptor biology". International Journal of Radiation Oncology, Biology, Physics. 59 (2 Suppl): 21–6. doi: 10.1016/j.ijrobp.2003.11.041 . PMID   15142631.
  11. ↑ Kumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. ISBN   978-0-7216-0187-8.
  12. 1 2 Chao J (2013-01-01), Rawlings ND, Salvesen G (eds.), "Chapter 624 - Mouse Kallikrein 9, Epidermal Growth Factor-binding Protein", Handbook of Proteolytic Enzymes (Third ed.), Academic Press, pp. 2830–2831, doi:10.1016/b978-0-12-382219-2.00624-4, ISBN   978-0-12-382219-2
  13. ↑ Satyanarayana U (2002). Biochemistry (2nd ed.). Kolkata, India: Books and Allied. ISBN   8187134801. OCLC   71209231.
  14. ↑ Dawson JP, Berger MB, Lin CC, Schlessinger J, Lemmon MA, Ferguson KM (September 2005). "Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface". Molecular and Cellular Biology. 25 (17): 7734–42. doi:10.1128/MCB.25.17.7734-7742.2005. PMC   1190273 . PMID   16107719.
  15. ↑ Fallon JH, Seroogy KB, Loughlin SE, Morrison RS, Bradshaw RA, Knaver DJ, et al. (June 1984). "Epidermal growth factor immunoreactive material in the central nervous system: location and development". Science. 224 (4653): 1107–9. Bibcode:1984Sci...224.1107F. doi:10.1126/science.6144184. PMID   6144184.
  16. 1 2 Dreux AC, Lamb DJ, Modjtahedi H, Ferns GA (May 2006). "The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis". Atherosclerosis. 186 (1): 38–53. doi:10.1016/j.atherosclerosis.2005.06.038. PMID   16076471.
  17. ↑ Stortelers C, Souriau C, van Liempt E, van de Poll ML, van Zoelen EJ (July 2002). "Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display". Biochemistry. 41 (27): 8732–41. doi:10.1021/bi025878c. PMID   12093292.
  18. ↑ Wong L, Deb TB, Thompson SA, Wells A, Johnson GR (March 1999). "A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling". The Journal of Biological Chemistry. 274 (13): 8900–9. doi: 10.1074/jbc.274.13.8900 . PMID   10085134.
  19. ↑ Berlanga J, Fernández JI, López E, López PA, del Río A, Valenzuela C, et al. (January 2013). "Heberprot-P: a novel product for treating advanced diabetic foot ulcer". MEDICC Review. 15 (1): 11–5. doi: 10.1590/s1555-79602013000100004 . PMID   23396236.
  20. ↑ Yang S, Geng Z, Ma K, Sun X, Fu X (June 2016). "Efficacy of Topical Recombinant Human Epidermal Growth Factor for Treatment of Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis". The International Journal of Lower Extremity Wounds. 15 (2): 120–5. doi:10.1177/1534734616645444. PMID   27151755. S2CID   43897291.
  21. 1 2 Martí-Carvajal AJ, Gluud C, Nicola S, Simancas-Racines D, Reveiz L, Oliva P, et al. (October 2015). "Growth factors for treating diabetic foot ulcers". The Cochrane Database of Systematic Reviews. 2015 (10): CD008548. doi:10.1002/14651858.CD008548.pub2. PMC   8665376 . PMID   26509249.
  22. ↑ Haddad T, Noel S, Liberelle B, El Ayoubi R, Ajji A, De Crescenzo G (January 2016). "Fabrication and surface modification of poly lactic acid (PLA) scaffolds with epidermal growth factor for neural tissue engineering". Biomatter. 6 (1): e1231276. doi:10.1080/21592535.2016.1231276. PMC   5098722 . PMID   27740881.
  23. ↑ Tenchurin T, Lyundup A, Demchenko A, Krasheninnikov M, Balyasin M, Klabukov I, et al. (2017). "Modification of biodegradable fibrous scaffolds with Epidermal Growth Factor by emulsion electrospinning for promotion of epithelial cells proliferation". Гены и клетки (in Russian). 12 (4): 47–52. doi:10.23868/201707029. S2CID   90593089.
  24. ↑ Del Angel-Mosqueda C, Gutiérrez-Puente Y, López-Lozano AP, Romero-Zavaleta RE, Mendiola-Jiménez A, Medina-De la Garza CE, et al. (September 2015). "Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro". Head & Face Medicine. 11: 29. doi: 10.1186/s13005-015-0086-5 . PMC   4558932 . PMID   26334535.
  25. ↑ Pache JC (2006-01-01). "Epidermal growth factors". In Laurent GJ, Shapiro SD (eds.). Encyclopedia of Respiratory Medicine. Oxford: Academic Press. pp. 129–133. doi:10.1016/b0-12-370879-6/00138-1. ISBN   978-0-12-370879-3 . Retrieved 2020-11-30.

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