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Finally, unbiased phosphoproteomics combined with kinase inhibition has revealed hundreds of novel GSK3 substrates [34], many of which have known or plausible roles in GLUT4 traffic including the regulator of GLUT4 endocytosis GAPVD1/GAPEX5 (GSK3 sites: S758 and T762 in mice) [106108], the early/recycling endosome regulator RBSN/Rabenosyn-5 (S225) [109], and the endosome-to-Golgi trafficking regulator GOLGA4/golgin-245 (T39 and S40) [110]

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[18] Enzymes Involved in Biosynthesis (in order of activity) [17] [18] GliZ: transcription factor that regulates expression of gli gene cluster GliP: non-ribosomal peptide synthetase that facilitates formation of cyclo-phenylalanyl-serine intermediate from serine and phenylalanine residues GliC: cytochrome P450 monooxygenase that adds hydroxyl group to the alpha carbon of the phenylalanine residue in the cyclo-phenylalanyl-serine intermediate GliG: glutathione S-transferase (GST) that adds two glutathione molecules forming a bis-glutathionylated intermediate GliK: gamma-glutamyl transferase that removes gamma-glutamyl moieties from glutathione additions GliJ: Cys-Gly carboxypeptidase that removes carboxyl moieties from glutathione additions GliI: aminotransferase that removes amino moieties from glutathione additions GliF: cytochrome P450 monooxygenase that adds hydroxyl group to the benzene residue and facilitates ring closure GliN/GliM: N-methyltransferase/O-methyltransferase that adds a methyl group to nitrogen to form the dithiol gliotoxin intermediate utilizing s-adenosyl methionine (SAM) in the reaction GliT: oxidoreductase thioredoxin that mediates closure of the disulfide-bridge GliA: Major Facilitator Superfamily transporter that secretes gliotoxin across cell membrane The exact roles of the enzymes GliC, GliF, GliM, and GliN and the steps in the biosynthetic pathway of these enzymes are still not completely understood in the biosynthesis of gliotoxin

These aggressive protocols typically run shorter durations

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