Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vasodilator-stimulated phosphoprotein (VASP) plays an important role in cGMP-induced platelet inhibition. Since VASP is an in vitro substrate for cGMP-dependent protein kinase (PKG), it has been presumed that VASP phosphorylation induced by cGMP is mediated by PKG. Here we show that, in human platelets, phosphorylation of VASP at Ser239 induced by either cGMP analogs or nitric oxide (NO) donor glyco-SNAP1 is inhibited by PKA inhibitors KT5720, PKI, Rp-Br-cAMPS, and H89, but not by PKG inhibitors KT5823 or Rp-pCPT-cGMPS. Unlike human platelets, cGMP analog-induced phosphorylation of VASP in mouse platelets is inhibited by both PKG and PKA inhibitors. Ineffectiveness of PKG inhibitors in inhibiting VASP phosphorylation in human platelets is not due to an inability to inhibit PKG, as these PKG inhibitors but not PKA inhibitors inhibit a different cGMP-induced intracellular signaling event: phosphorylation of extracellular signal-responsive kinase. Furthermore, PKA inhibitors reverse cGMP-induced inhibition of thrombin-induced platelet aggregation, whereas PKG inhibitors further enhance the inhibitory effect of cGMP analogs. Thus, PKA plays a predominant role in the cGMP-induced phosphorylation of VASP and platelet inhibition in human platelets.
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PMID:A predominant role for cAMP-dependent protein kinase in the cGMP-induced phosphorylation of vasodilator-stimulated phosphoprotein and platelet inhibition in humans. 1546 67

The Na+/K+ ATPase modulates the activity of many transporters in the liver, and maintains the ionic constancy of the intracellular milieu, preserving thus normal functioning of hepatocytes. Previous work showed that FTY720P, a sphingosine one phosphate receptor agonist used in the treatment of multiple sclerosis, exerts in HepG2 cells, an inhibitory effect on the activity of the ATPase, mediated via PGE2. This study is an attempt to identify the signaling molecules involved downstream of the prostaglandin. The activity of the ATPase was assayed by measuring the amount of inorganic phosphate liberated in presence and absence of ouabain, a specific inhibitor of the enzyme. The effect of FTY720P and PGE2 disappeared completely in presence of PF-04418948, a blocker of EP2 receptors, RpcAMP, an inhibitor of PKA, PD98059, an inhibitor of ERK, as well as in presence of PTIO, a nitric oxide synthase inhibitor, but was mimicked by butaprost, an EP2 agonist, dbcAMP, a cell permeable cAMP analogue, and SNAP1,a nitric oxide generator. PGE2 and dbcAMP increased the expression of phosphorylated ERK but not total ERK. This increase did not appear however in presence of PTIO, indicating that PKA is upstream of NO. It was concluded that FTY 720P induces PGE2 release which activates NOS leading to NO production and ERK activation. ERK then inhibits directly or indirectly the Na+/K+ ATPase.
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PMID:Signaling pathway involved in the inhibitory effect of FTY720P on the Na+/K+ ATPase in HepG2 cells. 2819 66