Structure-function relationship of the insulin-like growth factor-I receptor tyrosine kinase

• Published in: The Journal of biological chemistry Vol. 268; no. 31; pp. 23435 - 23440
• Main Authors: Grønborg, M, Wulff, B.S., Rasmussen, J.S., Kjeldsen, T, Gammeltoft, S
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 05-11-1993
• Subjects: 3T3 Cells; Animals; Base Sequence; Biological and medical sciences; Cell Cycle; Cell physiology; Fundamental and applied biological sciences. Psychology; Humans; In Vitro Techniques; Insulin-Like Growth Factor I - metabolism; Mice; Molecular and cellular biology; Molecular Sequence Data; Mutagenesis, Site-Directed; Oligodeoxyribonucleotides - chemistry; Phosphorylation; Phosphotyrosine; Receptor Protein-Tyrosine Kinases - metabolism; Receptor, IGF Type 1 - chemistry; Receptor, IGF Type 1 - metabolism; Recombinant Proteins; Signal Transduction; Structure-Activity Relationship; Tyrosine - analogs & derivatives; Tyrosine - chemistry; Signal transduction; Somatomedin C; Enzyme; Transferases; Insulin; Protein-tyrosine kinase; Structure function relationship; Hormonal receptor; Growth factor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(19)49481-7

Insulin-like growth factor I (IGF-I) and insulin receptors are structurally similar with ligand-stimulated tyrosine kinase
activity in their cytoplasmic domains. The function of the insulin receptor tyrosine kinase in signal transduction has been
studied extensively in contrast to the IGF-I receptor tyrosine kinase. In the present study we have analyzed the regulatory
function of the IGF-I receptor tyrosine kinase and carboxyl-terminal domains in mitogenic signaling by overexpression of mutant
IGF-I receptors in mouse NIH-3T3 fibroblasts. A mutant IGF-I receptor, in which 3 tyrosines (Tyr1131, Tyr1135, and Tyr1136)
analogous to the three major autophosphorylation sites in the insulin receptor kinase were replaced by phenylalanines, was
devoid of kinase activity in vivo and in vitro and inactive with respect to IGF-I internalization and stimulation of thymidine
incorporation. Another mutant IGF-I receptor, which lacks the 49 carboxyl-terminal amino acids (residues 1289-1337) of the
beta-subunit, was fully active. Our data suggest that the structure-function relationship of the IGF-I receptor tyrosine kinase
activation and signal transduction is similar to that of the insulin receptor.