Gene Section Mini Review Atlas Genet Cytogenet Oncol Haematol. 2009; 13(8) 559 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS IGF1R (insulin-like growth factor 1 receptor) Itay Bentov, Haim Werner Department of Human Molecular Genetics and Biochemistry, Sackler School of Medecine, Tel Aviv University,Tel Aviv 69978, ISRAEL (IB, HW) Published in Atlas Database: September 2008 Online updated version : http://AtlasGeneticsOncology.org/Genes/IGF1RID40928ch15q26.html DOI: 10.4267/2042/44533 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Other names: CD221; IGFIR; JTK13; MGC142170; MGC142172; MGC18216 HGNC (Hugo): IGF1R Location: 15q26.3 DNA/RNA Description The IGF1R gene contains 21 exons spanning approximately 100-kb of genomic DNA. Transcription The IGF1R mRNA is a 11242-base, single-stranded linear molecule. Various hormones and growth factors were shown to regulate IGF1R gene transcription. Specifically, growth factors and oncogenic agents associated with positive stimulation of cell division were shown to upregulate IGF1R gene expression whereas negative modulators of cell growth (e.g., tumor suppressors) usually cause a reduction in IGF1R gene expression. Growth factors that stimulate IGF1R gene transcription include, among others, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF). In addition, IGF1R gene expression is regulated by steroid hormones. Thus, estradiol was shown to increase, while progesterone decreased, IGF1R mRNA levels in breast cancer cells. Protein Description The IGF1R is a cell-surface tyrosine kinase receptor that is synthesized as a single polypeptide chain which is then processed to yield an around 180-kDa glycopeptide. The length of the IGF1R precursor is 1367 amino acids. Precursor chains include a 30-amino acid leader peptide rich in hydrophobic residues, which is involved in the transfer of the nascent protein into the endoplasmic reticulum. Partially processed proreceptors form disulfide-linked dimers that are subsequently glycosylated and proteolytically cleaved at a basic tetrapeptide sequence to yield mature α and β subunits. The mature heterotetramers have a β-α-α-β conformation. The α subunit is entirely extracellular and includes a cysteine-rich region and several potential N-linked glycosylation sites (Asn-X-Ser/Thr motifs). The cysteine-rich domain of the IGF1R is important for high-affinity IGF1 binding. The β subunit features a unique hydrophobic sequence that constitutes the transmembrane domain. The cytoplasmic portion of the β subunit contains a tyrosine kinase enzymatic domain. Inside this catalytic region there is a glycine-rich conserved element that participates in the transfer of the phosphate moiety of ATP to specific substrates. Expression The IGF1R is abundantly expressed in the embryo, with significant reduction in expression levels at adult stages. Localisation The IGF1R is essentially expressed by most organs and tissues. Very high levels are detected in brain. Extremely low levels are seen in liver, due to downregulation by hepatic IGF1. Function The IGF1R is involved in growth, development, and differentiation processes. The IGF1R displays a very