Recombinant Human Insulin-like growth factor I (IGF1)

Function

The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation (PubMed:21076856, PubMed:24132240). Ca(2+)-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb (By similarity). Acts as a ligand for IGF1R. Binds to the alpha subunit of IGF1R, leading to the activation of the intrinsic tyrosine kinase activity which autophosphorylates tyrosine residues in the beta subunit thus initiating a cascade of down-stream signaling events leading to activation of the PI3K-AKT/PKB and the Ras-MAPK pathways. Binds to integrins ITGAV:ITGB3 and ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and IGFR1 are essential for IGF1 signaling. Induces the phosphorylation and activation of IGFR1, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:19578119, PubMed:22351760, PubMed:23243309, PubMed:23696648). As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via promotion of STUB1/CHIP-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity)

Subcellular Location

Secreted

Disease Association

Insulin-like growth factor I deficiency (IGF1D) : An autosomal recessive disorder characterized by growth retardation, sensorineural deafness and intellectual disability. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

Forms a ternary complex with IGFR1 and ITGAV:ITGB3 (PubMed:19578119). Forms a ternary complex with IGFR1 and ITGA6:ITGB4 (PubMed:22351760, PubMed:23696648). Interacts with SH2D3C isoform 2 (PubMed:20881139). Forms a ternary complex with IGFBP3 and ALS (PubMed:35907924)

• Jansen M. et al. Sequence of cDNA encoding human insulin-like growth factor I precursor. — Nature (1983)
• de Pagter-Holthuizen P. et al. Organization of the human genes for insulin-like growth factors I and II. — FEBS Lett. (1986)
• le Bouc Y. et al. Complete characterization of the human IGF-I nucleotide sequence isolated from a newly constructed adult liver cDNA library. — FEBS Lett. (1986)
• Rotwein P. et al. Organization and sequence of the human insulin-like growth factor I gene. Alternative RNA processing produces two insulin-like growth factor I precursor peptides. — J. Biol. Chem. (1986)
• Rotwein P. et al. Two insulin-like growth factor I messenger RNAs are expressed in human liver. — Proc. Natl. Acad. Sci. U.S.A. (1986)
• Tobin G. et al. A novel human insulin-like growth factor I messenger RNA is expressed in normal and tumor cells. — Mol. Endocrinol. (1990)
• Steenbergh P.H. et al. Complete nucleotide sequence of the high molecular weight human IGF-I mRNA. — Biochem. Biophys. Res. Commun. (1991)
• Sandberg-Nordqvist A.-C. et al. Characterization of two cDNAs encoding insulin-like growth factor 1 (IGF-1) in the human fetal brain. — Brain Res. Mol. Brain Res. (1992)