Kinase of

Basically, AZT is anabohcaHy phosphorylated to AZT mono-, di-, and tri-phosphates by various enzymes (kinases) of a target ceU (159). AZT-triphosphate competes with other phosphorylated pyrimidine nucleosides for incorporation into HIV DNA by the viral reverse transcriptase. Incorporation of the AZT-triphosphate into reverse transcriptase results in viral DNA chain termination. Reverse transcriptase is essential in the repHcative cycle of HIV. 

Hunter, T., Plowman, G.D. The protein kinases of budding yeast six score and more. Trends Biochent. Sci. 

In contrast to the DNA damage checkpoint, the mitotic spindle checkpoint is essential for cell viability. Dierefore, targeting kinases of the spindle checkpoint including Bubl, BubRl, and Mpsl might be a valid strategy for anticancer treatment. 

PTKs can be subdivided into two large families, receptor tyrosine kinases (RTKs) and non-RTKs. The human genome encodes for a total of 90 tyrosine kinases of which 32 are nonreceptor PTKs that can be placed in 10 subfamilies (Fig. 1). All nonreceptor PTKs share a common kinase domain and usually contain several additional domains that mediate interactions with protein-binding partners, membrane lipids, or DNA (Table 1). These interactions may affect cellular localization and the activation status of the kinase or attract substrate proteins for phosphorylation reactions. 

The 2 -chloro and 2 -bromo congeners of either 748 (FIAC) or 758 (FMAU) are more cytotoxic than FIAC and FMAU, suggesting that these chloro and bromo nucleosides, in contrast to the 2 -fluoro compounds, are comparatively better substrates for deoxycytidine kinase of human lymphocytes than the substrates for viral-specific thymidine kinase. The disposition of the 2 -fluoro group may also be important from the biological viewpoint. It should be noted that the structural difference between RNA and DNA is at the 2 -position. The ribo type of analog (738) of FIAC is 10 times less effective in suppression of HSV replication than is FIAC. Thus Fox, and Watanabe and coworkers concluded that the 2 - up fluorine disposition and the species of the substituent at C-5 are the two important factors influencing antiviral activity. Nevertheless, the mechanism of action of 2 -deoxy-2 -fluorocytidine (737) on certain herpes viruses, including HSV-1... 

Phosphorylation by protein kinases of specific seryl, threonyl, or tyrosyl residues—and subsequent dephosphorylation by protein phosphatases—regulates the activity of many human enzymes. The protein kinases and phosphatases that participate in regulatory cascades which respond to hormonal or second messenger signals constimte a bio-organic computer that can process and integrate complex environmental information to produce an appropriate and comprehensive cellular response. 

A third group of MAPKs are p38 kinases, of which there are four subtypes a, [3, y, and 8. P38 MAPKs are activated by many stimuli including hormones, ligands for G-protein-coupled receptors and stresses [13,17]. P38 MAPK has been implicated in the pathological changes accompanying inflammatory and apoptotic processes of various cell types, including neurons [17] (see Ch. 35 for... 

Z -LYTE Invitrogen Phosphorylation by a kinase of dual labeled FRET peptide changes its susceptibility to proteolytic cleavage... 

Sevilla A, Santos CR, Barcia R, Vega FM, Lazo PA (2004a) c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRKl) and its cooperation with the N-terminal kinase of c-Jun (JNK). Oncogene 23(55) 8950-8958... 

Based on their substrate specificity, kinases have been divided into two broad classes serine/threonine- and tyrosine-specific kinases. Of the estimated 500 kinases, roughly one-fifth of these are tyrosine kinases. The two classes are further broken down and grouped by function, required cofactors, and substrates. ... 

Samson, L, Kerremans, L., Rozenski, J., Samyn, B., Van beeumen, J., and Herdewijn, P. Identification of a peptide inhibitor against glycosomal phospho-glycerate kinase of Trypanosoma bmcei by a synthetic peptide library... 

The indolin-2-one template, a feature of inhibitors of the receptor tyrosine kinases of Her-2, VEGF, and EGF, was used by GlaxoSmithKline scientists as a starting point to design a series of analogs from which the selective CDK-2 inhibitor 60 (IC50 = 0.06 xM) was identified. A thorough analysis of... 

Kinases Chkl play a significant role in the regulation of the G2/M cell cycle, so inhibitors of kinases of this class are promising antitumor agents (06BMC4792). Docking with the ATP-binding site of Chkl kinase has been performed for compound 312, and the experimental inhibition value IC n is 20.4 2.5 pM. 

Borner C, Wyss R, Regazzi R, Eppenberger U, Fabbro D (1987) Immunological quantitation of phospholipid/Ca -dependent protein kinase of human mammary carcinoma cells inverse relationship to estrogen receptors. Int ) Cancer 40 344-348... 

Chambers TC, Pohl J, Glass DB, Kuo JF (1994) Phosphorylation by protein kinase C and cyclic AMP-dependent protein kinase of synthetic peptides derived firom the linker region of human P-glycoprotein. Biochem J 299 309-315... 

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