Tyrosine kinase insulin receptor

Phospholipid Insulin Receptor Tyrosin Kinases Growth Factors... 

Vanadate (sodium orthovanadate or peroxovanadate) exhibits insulin-like effects in vitro (activation of insulin receptor tyrosine kinase, PI 3-kinase, Akt) and in vivo (diabetic rats, humans). These effects can be explained at least in part by the inhibition of phosphotyrosine phosphatases which deactivate the INSR tyrosine kinase. 

Hubbard, S. R., Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog, EMBO J., 16, 5572-5581, 1997. 

Holland W., T. Morrison, Y. Chang, N. Wiemsperger, and B.J. Stith (2004). Metaformin (glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase. Biochemical Pharmacology 67 2081-2091. 

The catalytic loop is the region of divergence between Ser/Thr and Tyr kinases. In cAPK and all Ser/Thr Kinases, Lysl68 interacts with the phosphate of ATP during catalysis [12]. The role of Lys is replaced by Arg [9] and the insulin receptor tyrosine kinase structure [3] shows Argl 136 in a similar position as Lys 168 in the active site of cAPK. 

Wilden, P.A. Kahn, C.R. The level of insulin receptor tyrosine kinase activity modulates the activities of phosphatidylinositol 3-kinase, microtubule-associated protein, and S6 kinases. Mol. Endocrinol., 8, 558-567 (1994)... 

InsRTK Insulin receptor tyrosine kinase the proto-oncogene ras... 

Figure 16.17 The insulin receptor, y signifies the tyrosyl residues that become phos-phorylated as a result of insulin action. (Reproduced by permission from Espinal). What is the role of the insulin receptor tyrosine kinase TIBS October 367-368, 1988.)...

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... 

G. S. Hotamisligil, P. Peraldi, A. Budavari, R Ellis, M. F. White and B. M. Spic eiman. IRS-l-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science, 271 (5249), 665-668, 1996. 

IRS-1 Couples the Insulin Receptor Tyrosine Kinase to a Ras-activated Signalling Cascade of Serine Kinases... 

In Xenopus o(x es (126,134), treatment with metformin has been shown to increase insulin receptor tyrosine kinase activity associated with activation of phospholipase C and increased levels of IPg and intracellular Ca. Thus metformin, through increasing receptor tyrosine kinase activity, may facilitate IRS protein phosphorylation and activation of phosphatidylinositol-3-kinase, leading to increased glucose uptake. 

On phosphorylation, the insulin receptor tyrosine kinase is activated. Because the two units of the receptor are held in close proximity to one another, additional sites within the receptor also are phosphorylated. These phosphorylatcd sites act as docking sites for other substrates, including a class of molecules referred to as insulin-receptor substrates (IJ S). From the IRS protein, the signal is conveyed through a series of membrane-anchored molecules to a protein kinase that finally leaves the membrane (Figure 14,20), lRS-1 and IRS-2 are two homologous proteins with a common... 

Figure 14.21 The modular structure of Insulin receptor substrates IRS-1 and IRS-2 This schematic view represents the amino acid sequence common to IRS-1 and lRS-2. Each protein contains a pleckstrin homology domain (which binds phosphoinositide lipids), a phospbotyrosine-binding domain, and four sequences that approximate Tyr-X-X-Met (YXXM). The latter are phosphorylated by the insulin receptor tyrosine kinase.

Leef J, Lamer J. Insulin-mimetic effect of trypsin on the insulin receptor tyrosine kinase in intact adipocytes. J Biol Chem 1987 262(30) 14837-14842. 

The favorable results in the case of the insulin receptor tyrosine kinase prompted the application of the bisubstrate analog approach to a serine/ threonine kinase [44]. Protein kinase A was selected because it had been... 

Inhibition of EGF-R tyrosine kinase by hypericin 1 was shown to be irreversible, non-competitive and time as well as temperature dependent. The IC50 increased from 0.75 pM in the dark to 44 nM with light illumination for 30 min. This effect was presumably due to a type I photosensitization mechanism since exclusion of oxygen did not alter the inhibition curve. Some Ser/Thr protein kinases (e.g., protein kinase A, casein kinase 1 and 2) and the enzyme 5 -nucleotidase were not inhibited even at concentrations > 100 pM [144]. However, the same authors recently reported that hypericin 1 in addition to protein kinase C also caused the light-dependent inhibition of certain other Ser/Thr kinases (e.g. protein kinase CK-2, mitogen-activated kinase) and the insulin receptor tyrosine kinase, while it was ineffective towards the cytosolic tyrosine kinases Lyn, Fgr, TPK-IIB and CSK. These results suggest that distantly related protein kinases could still share common reactive domains for the interaction with hypericin 1 [156]. In contrast to the above mentioned studies, Richter and Davies [157] observed no inhibition of EGF-induced tyrosine phosphorylation of the EGF-R in HN5 squamous carcinoma... 

Davis CM and Vincent JB (1997a) Chromium oligopeptide activates insulin receptor tyrosine kinase activity. Biochemistry 36 4382 -4385. 

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