Epidermal growth factor (EGF) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that stimulates

cell growth Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...

and differentiation by binding to its receptor, EGFR.

Human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

EGF is 6-k Da and has 53

amino acid residues Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single amino acid monomer may ...

and three intramolecular

disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

s. EGF was originally described as a secreted peptide found in the

submaxillary gland The paired submandibular glands (historically known as submaxillary glands) are major salivary glands located beneath the floor of the mouth. They each weigh about 15 grams and contribute some 60–67% of unstimulated saliva secretion; on stimula ...

s of

mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

and in human

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...

. EGF has since been found in many human tissues, including

platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

submandibular gland The paired submandibular glands (historically known as submaxillary glands) are major salivary glands located beneath the floor of the mouth. They each weigh about 15 grams and contribute some 60–67% of unstimulated saliva secretion; on stimula ...

(submaxillary gland), and

parotid gland The parotid gland is a major salivary gland in many animals. In humans, the two parotid glands are present on either side of the mouth and in front of both ears. They are the largest of the salivary glands. Each parotid is wrapped around the ma ...

. Initially, human EGF was known as urogastrone.

Structure

humans Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

, EGF has 53

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

(sequence NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWWELR), with a

molecular mass The molecular mass (''m'') is the mass of a given molecule: it is measured in daltons (Da or u). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The related quanti ...

of around 6

kDa The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...

. It contains three

disulfide bridges In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

(Cys6-Cys20, Cys14-Cys31, Cys33-Cys42).

Function

EGF, via binding to its cognate receptor, results in cellular proliferation, differentiation, and survival. Salivary EGF, which seems to be regulated by dietary inorganic

iodine Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...

, 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.

Biological sources

Epidermal growth factor can be found in

saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...

milk Milk is a white liquid food produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals (including breastfed human infants) before they are able to digestion, digest solid food. Immune factors and immune ...

tears Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all land mammals. Tears are made up of water, electrolytes, proteins, lipids, and mucins that form layers on the surface of eyes. The different types of ...

, and

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...

. It can also be found in the

submandibular glands The paired submandibular glands (historically known as submaxillary glands) are major salivary glands located beneath the floor of the mouth. They each weigh about 15 grams and contribute some 60–67% of unstimulated saliva secretion; on stimula ...

, and the

. The production of EGF has been found to be stimulated by

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...

Polypeptide growth factors

Polypeptide growth factors include:

Mechanism

EGF acts by binding with high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

epidermal growth factor receptor The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. The epidermal growth factor recept ...

(EGFR) on the

cell surface The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

. This stimulates ligand-induced dimerization, activating the intrinsic protein-tyrosine kinase activity of the receptor (see the second diagram). The

tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...

activity, in turn, initiates a

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

cascade that results in a variety of

biochemical Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...

changes within the cell – a rise in intracellular

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

levels, increased

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...

and

protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...

, and increases in the

expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...

of certain

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s including the gene for EGFR – that ultimately lead to

DNA synthesis DNA synthesis is the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. DNA is a macromolecule made up of nucleotide units, which are linked by covalent bonds and hydrogen bonds, in a repeating structure. DNA synthesis occur ...

and cell proliferation.

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: *

Heparin-binding EGF-like growth factor Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of proteins that in humans is encoded by the ''HBEGF'' gene. HB-EGF-like growth factor is synthesized as a membrane-anchored mitogenic and chemotactic glycoprotein. A ...

(HB-EGF) * transforming growth factor-α (TGF-α) * Amphiregulin (AR) *

Epiregulin Epiregulin (EPR) is a protein that in humans is encoded by the ''EREG'' gene. Structure Epiregulin consists of 46 amino acid residues. Its secondary structure contains approximately 30 percent of β-sheet in the strand. Some of the residues f ...

(EPR) *

Epigen Epigen also known as epithelial mitogen is a protein that in humans is encoded by the EPGN gene. Function The protein encoded by this gene is a member of the epidermal growth factor family. Members of this family are ligands for the epidermal ...

Betacellulin Betacellulin is a protein that in humans is encoded by the ''BTC'' gene located on chromosome 4 at locus 4q13-q21. Betacellulin was initially identified as a mitogen. Betacellulin, is a part of an Epidermal Growth Factor (EGF) family and function ...

(BTC) *

neuregulin-1 Neuregulin 1, or NRG1, is a gene of the epidermal growth factor family that in humans is encoded by the ''NRG1'' gene. NRG1 is one of four proteins in the neuregulin family that act on the EGFR family of receptors. Neuregulin 1 is produced in num ...

(NRG1) * neuregulin-2 (NRG2) * neuregulin-3 (NRG3) * neuregulin-4 (NRG4). All family members contain one or more repeats of the conserved amino acid sequence: CX₇CX_4-5CX_10-13CXCX₈GXRC Where C is

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

, G is

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

, R is

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...

, and X represents any

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

. This sequence contains six cysteine residues that form three intramolecular

s. Disulfide bond formation generates three structural loops that are essential for high-affinity binding between members of the EGF-family and their

cell-surface The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

receptors.

Interactions

Epidermal growth factor has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with

Medical uses

Recombinant human epidermal growth factor, sold under the brand name Heberprot-P, is used to treat

diabetic foot ulcer Diabetic foot ulcer is a major complication of diabetes mellitus, and probably the major component of the diabetic foot. Wound healing is an innate mechanism of action that works reliably most of the time. A key feature of wound healing is stepw ...

s. It can be given by injection into the wound site, or may be used topically. Tentative evidence shows improved wound healing. Safety has been poorly studied. EGF is used to modify synthetic scaffolds for manufacturing of

bioengineered Biological engineering or bioengineering is the application of principles of biology and the tools of engineering to create usable, tangible, economically-viable products. Biological engineering employs knowledge and expertise from a number o ...

grafts by emulsion

electrospinning Electrospinning is a fiber production method that uses Electrostatics, electric force to draw charged threads of polymer solutions or polymer melts up to fiber diameters in the order of some hundred nanometers. Electrospinning shares characterist ...

or surface modification methods.

Bone regeneration

EGF plays an enhancer role on 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 A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, an ...

engineering applications in

periodontics Periodontology or periodontics (from Ancient Greek , – 'around'; and , – 'tooth', genitive , ) is the specialty of dentistry that studies supporting structures of teeth, as well as diseases and conditions that affect them. The supporting ...

and oral implantology.

History

EGF was the second

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...

to be identified. Initially, human EGF was known as urogastrone. Stanly Cohen discovered EGF while working with

Rita Levi-Montalcini Rita Levi-Montalcini (, ; 22 April 1909 – 30 December 2012) was an Italian Nobel laureate, honored for her work in neurobiology. She was awarded the 1986 Nobel Prize in Physiology or Medicine jointly with colleague Stanley Cohen for th ...

at the

Washington University in St. Louis Washington University in St. Louis (WashU or WUSTL) is a private research university with its main campus in St. Louis County, and Clayton, Missouri. Founded in 1853, the university is named after George Washington. Washington University is r ...

during experiments researching nerve growth factor. For these discoveries Levi-Montalcini and Cohen were awarded the 1986

Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...

References

External links

Shaanxi Zhongbang Pharma-Tech Co., Ltd.-Supply of Epidermal Growth Factor
* EGF at th
Human Protein Reference Database
. *
EGF model in BioModels database
{{Growth factor receptor modulators Growth factors Morphogens