Guanine nucleotide phosphatase

Figure 2.13. Histamine H,-receptor-mediated inositol phospholipid hydrolysis. Stimulation of H,-receptors leads to activation of a phospholipase C. probably via a guanine-nucleotide regulatory protein (N). which catalyses the hydrolysis of phosphatidylinositol 4.5 -bisphosphate (PIP2) to give inositol trisphosphate (IP3) and 1,2-diacylglycerol (DG). IP3 is then broken down by phosphatases to eventually yield free myo-inositol. Lithium ions can inhibit the conversion of inositol 1-phosphate (IP,) to myo-inositol. Free inositol then interacts with CDP-diacylglycerol,formed by a reaction between phosphatidic acid (PA) and CTP, to yield phosphatidylinositol (PI). Phosphorylation of PI by kinases completes the lipid cycle by reforming PIP2. Modified from [147,148].

Gong MC, Cohen P, Kitazawa T, Ikebe M, Masuo M, Somlyo AP, Somlyo AV (1992) Myosin light chain phosphatase activities and the effects of phosphatase inhibitors in tonic and phasic smooth muscle. J Biol Chem 267 14662-14668 Gong MC, Fujihara H, Somlyo AV, Somlyo AP (1997) Translocation of rhoA associated with sensitization of smooth muscle. J Biol Chem 272 10704-10709 Gong MC, lizuka K, Nixon G, Browne JP, Hall A, Eccleston JF, Sugai M, Kobayashi S, Somlyo AV, Somlyo AP (1996) Role of guanine nucleotide-binding proteins - ras family or trimeric proteins or both - in Ca sensitization of smooth muscle. Proc Natl Acad Sci USA 93 1340-1345... 

The answer is c. (Katzung, p 933.) Resistance to thioguanine occurs because of an increase in alkaline phosphatase and a decrease in hypoxanthine-guanine phosphoribosyl transferase. These enzymes are responsible, respectively, for the increase in dephosphorylation of thiopurine nucleotide and the conversion of thioguanine to its active form, 6-thioinosinic acid. 

At the end of polymerization, the 5 end of the pre-mRNA molecule is modified by addition of a N-7-methyl guanine molecule (Fig. 6.15). The 5 terminal phosphate is removed by a phosphatase, and the resulting diphosphate 5 end reacts with the a-phosphate of GTP to form an unusual 5, 5 -triphosphate link (Cap 0). The 5 -cap also may be methylated by S-adenosylmethionine on the 2 -0H of the ribose sugar of the adjacent nucleotide (Cap 1) or on both ribose sugars in the 2 and 3 positions (Cap 2) (Fig. 6.15). This cap structure protects the 5 end of the primary transcript against attack by ribonucleases... 

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