Human insulin receptor

Kirkpatrick RB, Matico RE, McNulty DE, Strickler JE, Rosenberg M 1995 An abundantly secreted glycoprotein from Drosophila melanogaster is related to mammalian secretory proteins produced in rheumatoid tissues and by activated macrophages. Gene 153 147-154 Leconte I, Carpentier JL, Clauser E 1994 The functions of the human insulin receptor are affected in different ways by mutation of each of the four N-glycosylation sites in the fl subunit. J Biol Chem 269 18062-18071... 

Petruzzelli L, Herrera R, Arenas-Garcia R, Fernandez R, Bimbaum MJ, Rosen OM 1986 Isolation of a Drosophila genomic sequence homologous to the kinase domain of the human insulin receptor and detection of the phosphorylated Drosophila receptor with an anti-peptide antibody. Proc Natl Acad Sci USA 83 4710-4714 Podskalny J, McElduff A, Gorden P 1984 Insulin receptors on Chinese hamster ovary (CHO) cells altered insulin binding to glycosylation mutants. Biochem Biophys Res Commun 125 70-75... 

Figure 2.8. Scheme of a chimeric peptide with examples for each of the distinct domains. 0X26, anti-rat transferrin receptor monoclonal antibody (mAh) 84-15, anti-human insulin receptor mAh cHSA, cationized human serum albumin VIP, vasoactive intestinal polypeptide DALDA, dermorphin analogue NGF, nerve growth factor BDNF, brain-derived neurotrophic factor PNA, peptide nucleic acid (3-gal, (3-galactosidase. 

AUC, area under curve of plasma concentration Av, avidin NLA, neutral avidin SA, streptavidin cHSA, cationized human serum albumin HIR MAb, human insulin receptor mAb PS product, permeability surface area product. 

With regard to transport capacity, the introduction of the anti-human insulin receptor antibody (HIR MAb) 83-14 as a vector indicates the potential for future improvements in brain-specific delivery vectors. Compared to anti-TfR monoclonal antibodies, the brain de-hvery in primates is over 7-fold higher due to the high PS product of the HIR MAb. 

The first insight into the mechanism by which autophosphorylation controls the activity of the Tyr kinase was possible via the crystal structure of the Tyr kinase domain of the human insulin receptor (Hubbard et al., 1994). 

Hubbard, S.R., Wei, L., EUis, L. and Hendrickson, W.A. Crystal structnre of the tyrosine kinase domain of the human insulin receptor (1994) Natnre 372, 746-754... 

Axel Ullrich reported the sequencing of the human insulin receptor in Nature. Bill Rutter s UCSF team described the sequencing in Cell two months later. 

Coloma, M.J., et al. 2000. Transport across the primate blood-brain barrier of a genetically engineered chimeric monoclonal antibody to the human insulin receptor. Pharm Res 17 266. 

Yang-Feng TL, Francke U, Ullrich A. Gene for human insulin receptor localization to site on chromosome 19 involved in pre-B-cell leukemia. Science 1985 228(4700) 728-731. 

Zhang, B., Szalkowski, D., Diaz, E., Hayes, N., Smith, R., and Berger, J. (1994). Potentiation Insulin Stimulation of Phosphatidylinositol 3-Kinase by Thiazolidine-dione-Derived Antidiabetic Agents in Chinese Hamster Ovary Cells Expressing Human Insulin Receptor and L6 Myotubes./. Biol. Chem. 269, 25735-25741. 

KIT, Fit-3, and RET.13 It exhibited selectivity against other kinases, including MEK-1, ERK1, epidermal growth factor receptor and human insulin receptor (Table 1). 

PHOSPHORYLA TWN chronic myelongenous leukemia-associated KIO BCR-ABL Drosophila Kr protein hepatitis B virus core and precore antigens human c-fos protein human c-myc protein human EGF receptor human epidermal growth factor receptor (tyrosine kinase domain) human immunodeficiency virus p24 human immunodeficiency virus tat protein human insulin receptor 6-subunit human insulin receptor - tyrosine kinase domain... 

Homologues of the mammalian insulin receptor, IR, are the DAF-2 receptor in Caenorhabditis elegans and the IR-like receptor in Drosophila. TTie DAF-2 receptor shares 35% of its amino-acid sequence with the human insulin receptor and 34% with the insulin-like growth factor receptor-1. The tyrosine kinase domain of the DAF-2 receptor is 70% similar and 50% identical to the tyrosine kinase domain of the human insulin receptor. A ligand for DAF-2 has not yet been identified, but an insulin-like peptide is anticipated. Since a t5T>ical insulin receptor substrate, like lRS-1 or IRS-2, has not been found in C. elegans, it is assumed that a COOH-terminal extension of the DAF-2 receptor serves as a built-in receptor substrate, which when phosphorylated, helps to recruit signalling proteins. 

The dose relationship of the human insulin receptor with the IR-like receptors in... 

A process by which a substrate protein, usually a receptor, catalyzes selfphosphorylation, usually at a tyrosine residue. The mechanism can be either intramolecular (cis) or intermolecular (trans) although at least one system has been described with both cis and trans processes. See Cobb, M.H., Sang, B.-C., Gonzalez, R., Goldsmith, E., and Ellis, L., Autophosphorylation activates the soluble cytoplasmic domain of the insulin receptor in an intermolecular reaction, J. Biol. Chem. 264, 18701-18706, 1989 Frattali, A.L., Treadway, J.L., and Pessin, J.E., Transmembrane signaling by the human insulin receptor kinase. Relationship between intramolecular subunit trans- and c A-autophosphorylation and substrate kinase activation, J. Biol. Chem. 267, 19521-19528, 1992 Rim, J., Faurobert, E., Hurley,... 

Zliarig Y, Boado R, Pardridge W (2003b) Marked enhancement in gene expression by targedng die human insulin receptor. J Gene Med 5 157-163. 

N. Tennagels, D. Telting, S. Parva-RESCH, J.A. Maassen, and H.W. Klein, Identification of Ser(1275) and Ser(1309) as autophosphorylation sites of the human insulin receptor in intact cells, Biochem. Biophys. Res. Commun., 2001, 282, 387-393. 

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