InterPro domain: IPR009030

This growth factor receptor domain is a cysteine-rich region that is found in a variety of eukaryotic proteins that are involved in the mechanism of signal transduction by receptor tyrosine kinases. Proteins containing the growth factor receptor domain include the insulin-like growth factor-binding proteins (IGFBP) [ 1 ], the type-1 insulin-like growth-factor receptor (IGF-1R) [ 2 ], and members of the epidermal growth factor (EGF) receptor family [ 3 ], such as the receptor protein-tyrosine kinase Erbb-3 (ErbB3) [ 4 ]. The general structure of the growth factor receptor domain is a disulphide-bound fold containing a beta-hairpin with two adjacent disulphides.

IGFBPs control the distribution, function and activity of insulin-like growth factors (IGFs) IGF-I and IGF-II, which are key regulators of cell proliferation, differentiation and transformation. All IGFBPs share a common domain organisation, where the highest conservation is found in the N-terminal Cys-rich IGF-binding domain. The N-terminal domain contains 10-12 conserved cysteine residues.

IGF-1R is a member of the tyrosine-kinase receptor superfamily that is involved in both normal growth and development and malignant transformation. The Cys-rich domain is flanked by two L-domains, and together they contribute to hormone binding and ligand specificity, even though they do not bind ligand directly. The Cys-rich region is composed of eight disulphide-bonded modules, seven of which form a rod-shaped domain.

ErbB3 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. The extracellular region of ErbB3 is made up of two Cys-rich domains and two L-domains, arranged alternately [ 5 ]. The two L-domains and the first Cys-rich domain are structurally homologous to those found in IGF-1R. The two Cys-rich domains are extended repeats of seven small disulphide-containing modules. A beta-hairpin loop extends from the first Cys-rich domain to contact the C-terminal portion of the second Cys-rich domain, creating a large pore structure.

1. The interaction of insulin-like growth factor-I with the N-terminal domain of IGFBP-5. EMBO J. 20, 3638-44
2. Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor. Nature 394, 395-9
3. Insulin and epidermal growth factor receptors contain the cysteine repeat motif found in the tumor necrosis factor receptor. Proteins 22, 141-53
4. Structure of the extracellular region of HER3 reveals an interdomain tether. Science 297, 1330-3