Putative physiological substrates phosphorylated by PKGI and their functions
| Substrate | Function of Substrate Phosphorylation | Reference(s) |
|---|---|---|
| ATP-sensitive K+ channel | Increases channel activity | Han et al., 2001 |
| Bad | Protects against neuronal apoptosis | Johlfs and Fiscus, 2010 |
| Battenin (CLN3) | Targets this lysosomal protein to substrates | Michalewski et al., 1998 |
| β3-adrenergic receptor | Negates receptor effects, causing relaxation | Angelone et al., 2008 |
| Ca2+ channel (voltage-dependent; Cav1.2 L-type) α1C subunit | Affects cardiac action potential duration; modulates pacemaker activity; inhibits channel activity | Yang et al., 2007 |
| Ca2+ channel (voltage-dependent; Cav1.2 L-type) β2 subunit | Affects cardiac action potential duration; modulates pacemaker activity; inhibits channel activity | Yang et al., 2007 |
| Ca2+ channel, L-type, α1c subunit | Inhibits Ca2+ current | Jiang et al., 2000 |
| Ca2+-activated K+ channel (α-subunit, cslo-α) | Opens channel, causing muscle relaxation | Fukao et al., 1999 |
| Ca2+-sensitive K+ channel (Hslo) | Activates channel | Alioua et al., 1998 |
| Calponin homology-associated smooth muscle protein (CHASM) | Desensitizes protein to Ca2+ | Borman et al., 2004 |
| cAMP-dependent protein kinase regulatory subunit type I (PKA RI) | Disrupts inhibitory interaction with catalytic subunit; affects cAMP binding | Geahlen et al., 1981 |
| cGMP-dependent protein kinase anchoring protein 42 (GKAP42) | Promotes germ cell developmenta | Yuasa et al., 2000b |
| cGMP-dependent protein kinase type I-α (PKGIα) | Relieves autoinhibition; sensitizes kinase to cAMP and cGMP binding; targets PKGIα for ubiquitination | Hofmann and Flockerzi, 1983; Busch et al., 2002; Dey et al., 2009 |
| cGMP-dependent protein kinase type I-β (PKGIβ) | Increases basal activity; increases sensitivity to cGMP and cAMP; controls kinase localization | Smith et al., 1996; Collins and Uhler, 1999 |
| Cysteine-rich protein 2 (CRP2) [also known as cysteine-rich LIM-only protein 4 (CRP4)]b | Regulates cytoskeletal organizationa and pain perception; increases transcription of smooth-muscle related genes | Huber et al., 2000; Zhang et al., 2007; Schmidtko et al., 2008 |
| Cystic fibrosis transmembrane conductance regulator (CFTR) | Activates Cl− channel | Picciotto et al., 1992 |
| Formin homology-domain containing protein-1 (FHOD-1) | Affects cytoskeletal arrangement | Wang et al., 2004 |
| GABA-A receptor | —a | Leidenheimer et al., 1996; Nugent et al., 2009 |
| G-septin | Facilitates neuronal signal transductiona | Xue et al., 2000 |
| G-substratec | Participates in cerebellar function; activates protein phosphatase inhibitor; promotes long-term depression | Aitken et al., 1981; Endo et al., 1999, 2003 |
| Guanylyl cyclase, soluble | Desensitizes guanylyl cyclase to activators | Zhou et al., 2008 |
| 27-kDa Heat shock protein (HSP27) | Effects platelet function | Butt et al., 2001 |
| 60- and 70-kDa Heat shock proteins (HSP60, HSP70) | Prevents apoptosis; inhibits peroxynitrite production | Li et al., 2005; Chan et al., 2007 |
| Histone | —a | Glass and Krebs, 1979, 1982 |
| Inositol triphosphate receptor (IP3R) | Decreases Ca2+ release from IP3-receptive storehouses | Haug et al., 1999; Murthy and Zhou, 2003 |
| Inositol triphosphate receptor-associated PKG substrate isoform A (IRAGa)c | Decreases Ca2+ release from IP3-receptive storehouses | Schlossman et al., 2000; Ammendola et al., 2001 |
| IRAGb | Decreases Ca2+ release from IP3-receptive storehouses | Casteel et al., 2008 |
| Large conductance calcium-activated potassium channel (BKCa)c | Increases probability of channel opening; hyperpolarizes cells | Sausbier et al., 2000 |
| LIM and SH3 domain protein (LASP-1) | Induces translocation from membrane to cytosol; reduces interaction with actin | Butt et al., 2003; Keicher et al., 2004 |
| MEKK1 | Activates MEKK1 kinase activity | Soh et al., 2001 |
| Myosin phosphatase small regulatory subunit (M20) | Impedes myosin phosphatase interaction with phospholipids | Nakamura et al., 1999 |
| Myosin phosphatase large regulatory subunit (MYPT1)c | Impedes myosin phosphatase interaction with phospholipids; inhibits Rho kinase thereby inhibiting myosin phosphatase; decreases Ca2+ sensitization | Nakamura et al., 1999; Wooldridge et al., 2004 |
| Na+/K+ ATPase α-subunit | Stimulates ATPase activity | Fotis et al., 1999 |
| NC-1.1 receptor | Regulates natural cytotoxicitya | Holmgreen et al., 1997 |
| p21-activated kinase 1 (Pak) | Regulates cell morphology and Pak localization | Fryer et al., 2006 |
| Phosphodiesterase 5c | Increases cGMP hydrolysis; regulates cGMP binding to allosteric and catalytic binding sites | Corbin et al., 2000; Murthy et al., 2001; Rybalkin et al., 2002; Wilson et al., 2008 |
| Phospholambanc | Increase Ca2+ uptake by Serca [sarco(endo)plasmic reticulum Ca2+-ATPase] | Lalli et al., 1999 |
| Phospholipase A2 (PLA2) | Protects against PLA2-induced cell death | Chalimoniuk et al., 2009 |
| Phospholipase C β2 (PLCβ2) | —a | Xia et al., 2001 |
| Phospholipase C β3 (PLCβ3) | Reduces IP3 production | Xia et al., 2001 |
| pH-sensitive K+ channel | Hyperpolarizes basal forebrain cholinergic neurons | Kang et al., 2007 |
| Protein phosphatase inhibitor 1 (PPI-1) | Inhibits phosphatase activity | Tokui et al., 1996 |
| Rap1 GTP-ase activating protein 2-α (Rap1GAP2α)b | No detected effect in GTPase activity | Schultess et al., 2005 |
| Rap1GAP2βb | No detected effect in GTPase activity | Schultess et al., 2005 |
| Regulator of G protein signaling 2 (RGS2)c | Increases GTPase activity; inhibits IP3 production | Tang et al., 2003; Sun et al., 2005 |
| RGS4 | Decreases GTPase activity and phosphoinositol (PI) hydrolysis | Huang et al., 2007 |
| RhoAc | Decreases RhoA activity; regulates RhoA translocation; decreases contraction; controls vesicle trafficking; reduces myosin light chain (MLC) phosphorylation | Sawada et al., 2001; Ellerbroek et al., 2003; Murthy et al., 2003 |
| Ryanodine receptor | Regulates ryanodine binding to receptor | Takasago et al., 1991 |
| Septin-3b | Regulates septin localizationa | Xue et al., 2004 |
| Serotonin transporter (SERT)b | Increases serotonin (5-HT) uptake | Ramamoorthy et al., 2007; Zhang et al., 2007 |
| Smooth muscle light chain phosphatase (SMPP-1M) | Facilitates relaxation of smooth muscle | Lee et al., 1997 |
| Smoothelin-like protein 1 (SMTNL1) | Affects muscle fiber response to exercise | Wooldridge et al., 2008 |
| Splicing factor 1 | Interferes with pre-mRNA intron splicing | Wang et al., 1999 |
| Steroidogenic acute regulatory protein (StAR) | Increases androgen production | Andric et al., 2007 |
| Telokinc | Inhibits myosin light chain kinase (MLCK) activity; destabilizes myosin; mediates cGMP-induced relaxation | Walker et al., 2001 |
| Thromboxane A2 receptor 1α (TPα)b | Desensitizes receptor to thromboxane stimulationa | Yamamoto et al., 2001; Kelley-Hickie et al., 2007 |
| Titin N2BA and N2B | Affects sarcomere rigidity | Krüger et al., 2009 |
| Transient receptor potential Ca2+ channel isoform 3 (TRPC3)b | Decreases Ca2+ influx | Kwan et al., 2004 |
| Transient receptor potential Ca2+ channel isoform 6 (TRPC6) | Decrease Ca2+ influx | Koitabashi et al., 2010 |
| Troponin I | Desensitizes protein to Ca2+ | Layland et al., 2002 |
| Tyrosine hydroxylase | Decreases catecholamine synthesisa | Rodríguez-Pascual et al., 1999 |
| Vasodilator-stimulated phosphoprotein (VASP) | Regulates actin cytoskeleton and vesicle trafficking; controls K+ efflux from cells through ATP-sensitive channel | Butt et al., 1994; Cook and Haynes, 2007 |
| Vimentinc | Controls cytoskeleton intermediate filament dynamics | Wyatt et al., 1991; Pryzwansky et al., 1995 |