PKA, Protein kinase

PKA Protein kinase A or cAMP-dependent protein kinase... 

Figure 1.11 Pathways involved in phospholipase C (PLC) cellular signalling. PKA, protein kinase A or cAMP-dependent protein kinases PKC, protein kinase C PI, phosphatidylinositol PIP2, phosphatidylinositol bis-phosphate IP3, inositol triphosphate IP, inositol phosphate DAG, diacylglycerol.

Fig. 8.1 A schematic diagram illustrating the involvement of NF-k I in gpl20, ROS, NO, PG, IL-1/3 and TNF-a-mediated neurotoxicity. NMDA-R, N-Methyl-D-aspartate receptor, cPLA2, cytosolic phospholipase A2 lyso-PtdCho, lysophosphatidylcholine AA, arachidonic acid cAMP, cyclic adenosine monophosphate PKA, protein kinase A TNF-a, tumor necrosis factor-a TNF-a-R, TNF-a-receptor IL-1/8, interleukin-1 /3 IL-l/i-R, IL-1/8-receptor, IL-6, interleukin-6 MARK, mitogen-activated protein kinase NO, nitric oxide PG, prostaglandins EP-R, prostaglandin receptors NF-kB, nuclear factor-icB NF-kB-RE, nuclear factor-/cB-response element I/cB, inhibitory subunit of NF-icB HIV-1, human immunodeficiency virus type 1 gpl20, HIV-1 coat glycoprotein COX-2, cyclooxygenase-2 iNOS, inducible nitric oxide synthase SPLA2, secretory phospholipase A2 SOD, superoxide dismutase MMP, matrix metalloproteinase and VCAM-1, vascular adhesion molecule-1...

The nonproline-directed protein kinases (NPDPKs) such as tau-tubulin kinase 1 and 2, protein kinase A (PKA), protein kinase C (PKC), PKB/AKT, calmodulin (CaM) kinase II, MARK kinases, or CK I and n that modify residues close to acidic residues mainly in exons 2 and 3. NPDPKs modify Ser or Thr residues that are not followed by prolines (Kitano-Takahashi et al., 2007 Sergeant et al.,... 

PKA Protein kinase A cAMP-dependent kinase pKa, acid dissociation constant... 

Figure 2. Regulation of eNOS. eNOS can be regulated in a number of ways one of which concerns its association with caveolin-1, the coat protein of caveolae, resulting in inhibition of NOS activity. This inhibition of eNOS is reversed by binding of calcium/calmodulin (Ca VCaM) to the enzyme removing this inhibitoiy interaction with caveolin-1. Also eNOS can be phosphorylated on serine residues by a number of kinases such as protein kinase C (PKC), protein kinase A (PKA), protein kinase B (Akt/PKB) or AMP activated protein kinase (AMPK) resulting in activation (+) or inhibtion (-) of eNOS activity. eNOS can also associate with heat shock protein 90 (Hsp90) leading to activation of the enzyme.

The regulation of eNOS activity by phosphorylation is a well documented subject as the eNOS protein possess several consensus sequences for phosphorylation by protein kinase A (PKA), protein kinase C (PKC), protein kinase B (Akt/PKB) and AMP-activated protein kinase (AMPK). The eNOS enzyme has been reported to be phosphorylated on threonine, serine and t50 osine residues in response to various agonists. Many studies have shown that phosphorylation of eNOS on serine 1177 leads to an activation of eNOS [26-29], whereas phosphorylation on threonine 495 inactivates eNOS as this site is in the Ca Vcalmodulin binding domain [26]. Fleming et al. (2001) demonstrated that bradykinin (100 nM) increased eNOS activity in both porcine coronary artery endothelial cells (PCAE) and HUVEC via dephosphorylation of threonine 495 and phosphorylation of serine 1177 [30]. The bradykinin-induced phosphorylation of serine 1177 was abolished in the presence of a calmodulin dependent kinase II inhibitor whilst the dephosphorylation of threonine 495 was abolished by a protein phosphatase I inhibitor [30]. Harris et al. (2001) documented in BAEC that bradykinin (1 pM)-induced eNOS activity was mediated by activation of Akt/PKB [31] (see section 1.2.2) resulting in NOS phosphorylation at serine 1179 (bovine sequence) and a de-phosphorylation at threonine 497 mediated by calcineurin phosphatase. Typically, phosphorylation of eNOS at either of these sites is coordinated with dephosphorylation at the alternate site. 

Fig. 3. Summary of key mechanisms of action through which a model adrenotoxicant (indicated by a black star) could disrupt the synthesis of corticosteroids. References presenting data in support of this model are given in the text. ACTH, adrenocorticotropic hormone Rc, receptor G, G-protein AC, adenylyl cyclase Ca, calcium ATP, adenosine triphosphate cAMP, cyclic adenosine monophosphate PKA, protein kinase A StAR, Steroid acute regulatory protein SCC, P450SCO, cholesterol side chain cleaving enzyme 11/3, 11/3-hydroxylase 17a, 17a-hydroxylase 3/3-HSD, 3/3-hydroxysteroid-5A-steroid dehydrogenase C21, 21-hydroxylase ER, endoplasmic reticulum.

Fig. 3. Phosphorylation of glucose and fructose. Hxkl Hexokinase PI Hxk2 hexokinase PII Glk glucokinase Pgi phosphoglucose isomerase Pfk phosphofructokinase Fbp fructose-1,6-bisphosphatase Pka protein kinase A...

Fig. 2. NMDA receptor interactions mediated independently of PSD-95. Cl, C2 are alternatively spliced segments of the NRl cytoplasmic tail. Black tilled ovals represent actin-binding domains of a-actinin and spectrin. CaM = Ca-+/calmodulin CaMKlI = calmodulin-dependent kinase type II PPI = protein phosphatase I PKA = protein kinase A NF-L = neurofilament-L.

Fig. 4 Assays for G-protein-coupled receptors. The two main ciasses are binding and functional assays. Binding assays detect compounds that are ligands of the receptor. Functional assays probe the signaling of the receptor within the cell. Gs/i and Gq/i, G-proteins PLC, phospholipase C AC, adenylyl cyclase DAG, diacylglycerol cAMP, cyclic adenosine monophosphate PKC, protein kinase C PKA, protein kinase A (PKA) lns(l,4,5)P3, inositol phosphates P-CREB, phosphorylated cAMP response element binding protein CRE, cAMP regulatory element.

The abbreviations denote pAR, P-adrenergic receptor PARK, P-adrenergic receptor kinase AC, adenylyl cyclase PKA, protein kinase A PhD, phosducin. 

AP,4-aminopyridine cAMP, cyclic adenosine monophosphate extracell., extracellular GABA, y-aminobutyric acid PKA, protein kinase A. In this exceptional study, cannabinoids did not decrease glutamate release, but increased it. 

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