1. cGMP-dependent Protein Kinase Signalling Pathways Produced by Dr. Steven Pelech Kinexus Bioinformatics Corporation Copyright 2010

2. PKG Signalling PDK1PKG T58 T516 ? PKC  cGMP

3. S1105 S23 PLCB3 T1122 PDE5A S106 GUCY1A3 S64 eNOS S1177 PKG Signalling PDK1PKG T58 T516 ? PKC  cGMP

4. S1105 S23 PLCB3 T1122 PDE5A S106 GUCY1A3 S64 eNOS S1177 NO PKG Signalling PDK1PKG T58 T516 ? PKC  cGMP

5. S1105 S23 PLCB3 T1122 DAG IP 3 PDE5A S106 GUCY1A3 S64 eNOS S1177 NO PKG Signalling PDK1PKG T58 T516 ? PKC  cGMP Ca 2+

6. PKG Signalling www.phosphoNET.ca Substrate Short Name Substrate Full NameProteinTypeSubstrate Swissprot Phospho- site Effect of Phosphorylation Kinase Affecting All Kinases Affecting Phosphatase Affecting eNOSEndothelial nitric oxide synthetase SynthetaseP29474S1177Phosphorylation increases enzymatic activity of eNOS. PKG1PKACa, PKBa/Akt1, PKG1 GUCY1A3Soluble guanylate cyclaseCyclaseQ02108S64Phosphorylation inhibits cyclase activity. PKG1 PDE5AcGMP phosphodiesterase 5 PhosphodiesteraseO76074S106Phosphorylation increases phosphodiesterase activity. PKG1PKACa, PKG1PPP1CA PKG1cGMP-dependent protein kinase 1, alpha Protein-serine kinase, AGC group, PKG family Q13976T58Phosphorylation increases phosphotransferase activity and affinity for cGMP PKG1PKCa, PKG1 PLCB31-phosphatidylinositol-4,5- bisphosphate phosphodiesterase beta 3 Enzyme, phospholipid phospholipase C, phosphatidylinositol- specific Q01970S1105Phosphorylation inhibits of G-protein-activated PLC- beta3 activity. PKG1 PLCB31-phosphatidylinositol-4,5- bisphosphate phosphodiesterase beta 3 Enzyme, phospholipid phospholipase C, phosphatidylinositol- specific Q01970S26Phosphorylation inhibits of G-protein-activated PLC- beta3 activity. PKG1 PLCB31-phosphatidylinositol-4,5- bisphosphate phosphodiesterase beta 3 Enzyme, phospholipid phospholipase C, phosphatidylinositol- specific Q01970T1122Phosphorylation inhibits of G-protein-activated PLC- beta3 activity. PKG1 cGMP-dependent protein kinase 1, alpha Protein-serine kinase, AGC group, PKG family Q13976T516Phosphorylation increases phosphotransferase activity. ??