Structure and function of the type 1 insulin-like growth factor receptor

Citation
Te. Adams et al., Structure and function of the type 1 insulin-like growth factor receptor, CELL MOL L, 57(7), 2000, pp. 1050-1093
Citations number
388
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELLULAR AND MOLECULAR LIFE SCIENCES
ISSN journal
1420-682X → ACNP
Volume
57
Issue
7
Year of publication
2000
Pages
1050 - 1093
Database
ISI
SICI code
1420-682X(200007)57:7<1050:SAFOTT>2.0.ZU;2-O
Abstract
The type 1 insulin-like growth factor receptor (IGF-IR), a transmembrane ty rosine kinase, is widely expressed across many cell types in foetal and pos tnatal tissues. Activation of the receptor following binding of the secrete d growth factor ligands IGF-1 and IGF-2 elicits a repertoire of cellular re sponses including proliferation, and the protection of cells from programme d cell death or apoptosis. As a result, signalling through the IGF-IR is th e principal pathway responsible for somatic growth in foetal mammals, where as somatic growth in postnatal animals is achieved through the synergistic interaction of growth hormone and the IGFs. Forced overexpression of the IG F-IR results in the malignant transformation of cultured cells: conversely, downregulation of IGF-IR levels carl reverse the transformed phenotype of tumour cells, and may render them sensitive to apoptosis in vivo. Elevated levels of IGF-IR are observed in a variety of human tumour types, whereas e pidemiological studies implicate the IGF-I axis as a predisposing factor in the pathogenesis of human breast and prostate cancer. The IGF-IR has thus emerged as a therapeutic target for the development of antitumour agents. R ecent progress towards the elucidation of the three-dimensional structure o f the extracellular domain of the IGF-IR represents an opportunity for the rational assembly of small molecule antagonists of receptor function for cl inical use.