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Epidermal Growth Factor: Structure and Synthesis

المؤلف:  Norman, A. W., & Henry, H. L.

المصدر:  Hormones

الجزء والصفحة:  3rd edition , p363-364

2026-05-25

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The amino acid sequences of the founding member of this family, epidermal growth factor (EGF), as well as that of a closely related member, transforming growth factor α (TGFα) are shown in Figure 1. All the members contain the conserved amino acid sequence CX₇CX_4–5CX_10–13CXCX₈C where X is any amino acid. The six cysteine residues in this sequence participate in three intramolecular disulfide bonds, forming three structural loops that are characteristic of these growth factors and necessary for high-affinity binding to their receptor(s).

Fig1. Structural features of the family of epidermal growth factors. The figure shows the amino acid sequences of two closely related members of the EGF family, EGF itself and TGFα. Highly conserved among all the members of this family are the three disulfide bonds (orange) which result in the characteristic loop structure of the peptides. There are also three highly conserved amino acids (green) in this portion of all members of this peptide family, leading to the overall motif: CX₇CX_4–5CX _10–13CXCX₈C where X is any amino acid.

All members of the EGF family of growth factors, listed in Table 1, are synthesized as pro-proteins with a signal sequence directing it to the plasma membrane. A single membrane-spanning region anchors EGF to the membrane, generating an N-terminal extracellular domain and an intracellular cytoplasmic tail. Cleavage of the extracellular domain to release the soluble active form of the growth factor is carried out by a member of the ADAM (a disintegrin and metalloproteinase) family of metalloproteinases. For example, ADAM17 has been implicated in the cleavage HB-EGF, TGFα, amphiregu lin, whereas ADAM10 catalyzes the release of soluble betacellulin. This process is highly regulated by other cell signaling systems in ways that are not yet completely understood. Although there is some in vitro evidence that the anchored form of EGF-related growth factors can activate receptors on nearby cells (termed a juxtacrine effect), it is well accepted that the release of the soluble form from the cell membrane is necessary for its physio logical role in normal development and in tumorigenesis.

Table1. Members of the EGF Family