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Unformatted text preview: ize crosstalk •  Mul5ple signals oXen required for ac5vity Andres Kreegipuu, Nikolaj Blom, Søren Brunak, Jaak Järv Sta5s5cal analysis of protein kinase specificity determinants FEBS LeOers, Volume 430, Issues 1–2, 23 June 1998, Pages 45–50 Kinases Integrate Cellular Signals Kinases (here Src) bind ATP-Mg2+ SH2 and SH3 are regulatory domains hOp://www.cellsignal.com/reference/landscapes/rtk.html hOp://www.cellsignal.com/reference/landscapes/rtk.html Protein Kinases Tyrosine kinases Protein HH N O Protein Protein ATP OH HH N O Protein O ADP O P OH OH Protein Kinases Serine- threonine kinases HH N Protein O ATP Serine Protein HH N H3C Protein Protein OH HH N O O OH Protein Threonine ATP ADP Protein O ADP Protein O HH N H3C P OH OH O Protein O O P OH OH Cataly5c Mechanism Enzymatic catalysis: kinases N- lobe αC helix C- lobe Inhibitor or pseudosubstrate has an alanine instead of serine in the active site Protein Kinase A Lecture 4 Pharm Sci/Chem 177, University of California, Irvine Enzymatic catalysis: kinases N- lobe αC helix Protein kinase A is activated by cyclic AMP (10 nM) C- lobe Protein Kinase A Cyclic AMP is an intracellular messenger mediating the...
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