+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Differential activation of insulin receptor isoforms by insulin-like growth factors is determined by the C domain

, : Differential activation of insulin receptor isoforms by insulin-like growth factors is determined by the C domain. Endocrinology 147(2): 1029-1036

The actions of IGF-I and IGF-II are thought to be largely due to their activation of the IGF-I receptor. However, IGF-II can also bind with high affinity to, and effectively activate, an isoform of the insulin receptor (IR-A) that lacks a sequence at the carboxyl-terminal end of the extracellular alpha subunit due to the alternative splicing of exon 11. This isoform is poorly activated by IGF-I. Here, we show that IGF-II, but not IGF-I, induces potent autophosphorylation of residues Y1158, Y1162, and Y1163 in the activation loop of the kinase domain and tyrosine 960 in the juxtamembrane region of both IR-A and IR-B (exon 11+) isoforms. We have also found, by using IGF chimeras, that the C domain of IGF-II completely accounts for the ability of IGF-II to stimulate IR autophosphorylation compared with IGF-I. We further show that the C domains are responsible for the differential abilities of IGF-II and IGF-I to activate phosphorylation of insulin receptor substrate-1 and Akt, as well as their ability to induce migration and cell survival via the IR-A. Finally, we show for the first time that IGF signaling through the IR-A can protect cells from butyrate-induced apoptosis. In summary, our studies define the structural determinants that allow potent IGF-II signaling and regulation of cellular functions through the IR-A and provide novel insights into IGF signaling via the IR.


PMID: 16239300

DOI: 10.1210/en.2005-0736

Other references

Finkenwirth, P.; Schick, D.; Horger, M.S.; Fend, F.; Lauer, U.M.; Gregor, M.; Bitzer, M., 2009: Thrombotic microangiopathy under an effective treatment with gemcitabine. A 67-year-old male patient with a pancreatic carcinoma and hepatic metastases was admitted with progressive dyspnea and anuria. Previously he had received five cycles of a palliative chemotherapy with gemcitabine and responded well with a reductio...

Gilev A.P., 1969: The problem of central serotonin reactive structures in large laboratory animals. Izvestiya Sibirskogo Otdeleniya Akademii Nauk SSSR Seriya Biologo-Meditsinskikh Nauk (1): 107-115

Roth L.; Dinu I.V.; Chirita P.; Georgescu L.; Tudose N., 1969: Pancytopenia associated with total situs inversus fanconi syndrome in the adult. Medicina Interna (Bucharest) 21(12): 1503-1510

Morini, S.; Melai, M., 2005: Net CO2 exchange rate of in vitro plum cultures during growth evolution at different photosynthetic photon flux density. CO2 concentration was monitored during three 15-day subculturing cycles in vessels containing actively proliferating plum cultures of Prunus cerasifera, clone Mr.S. 2/5. The effects of two photosynthetic photon flux density regimes: 50+or-5 micro...

Xu, Z-Sheng.; Lee, B.Kwon.; Park, D-Woo.; Lee, S-Whan.; Kim, Y-Hak.; Lee, C.Whan.; Hong, M-Ki., 2010: Relation of plaque size to compositions as determined by an in vivo volumetric intravascular ultrasound radiofrequency analysis. As the plaques have enlarged, the changes in specific plaque compositions have not been sufficiently investigated. We evaluated the relation of plaque size to each plaque component (fibrotic, fibrofatty, dense calcium, and necrotic core) in 244 pa...

Guerin, C.; Eisenmann, V., 1994: Les tapirs (Mammalia, Perissodactyla) du Miocene superieur d'Europe occidentale. Geobios (Villeurbanne): 271: 113-127

Lowe, G.; Potter, B.V., 1981: The stereochemical course of yeast hexokinase-catalysed phosphoryl transfer by using adenosine 5'[gamma(S)-16O,17O,18O]triphosphate as substrate. Adenosine 5'[gamma(S)-16O, 17O, 18O]triphosphate has been synthesized and used to determine the stereochemical course of phosphoryl transfer catalysed by yeast hexokinase. The chirality at phosphorus of the D-glucose 6-[16O,17O,18O]phosphate...

Huang; Luo, 1994: Light quark dependence of the Isgur-Wise function from QCD sum rules. Physical Review. D, Particles and Fields 50(9): 5775-5780

Frost, G.J., 1987: The organisation of clinical paediatric examinations. Medical Teacher 9(3): 317-323

Zardi, O.T.sti,, A.G.orgi, G.V.nditti, G.F.ntanelli,, A., 1969: Epidemiologic interdependence between human and animal influenza viruses. Zooprofilassi 24 (2 3) 99-107