Protein A Induces NO Production: Involvement of Tyrosine Kinase, Phospholipase C, and Protein Kinase C

1998 ◽  
Vol 250 (2) ◽  
pp. 425-429 ◽  
Author(s):  
Shradha Goenka ◽  
Tanya Das ◽  
Gaurisankar Sa ◽  
Prasanta K. Ray
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Phospholipase C ◽  
Protein A ◽  
No Production ◽  
Kinase C

Protein A-Activated rat Splenic Lymphocyte Proliferation Involves Tyrosine Kinase-Phospholipase C-Protein Kinase C Pathway

2000 ◽  
Vol 22 (1) ◽  
pp. 75-90 ◽  
Author(s):  
Tanya Das ◽  
Gaurisankar Sa ◽  
V. Subbulakshmi ◽  
S. Subramaniam ◽  
Parimal C. Sen ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Phospholipase C ◽  
Lymphocyte Proliferation ◽  
Protein A ◽  
Splenic Lymphocyte ◽  
C Protein ◽  
Kinase C

Role of phospholipase C, protein kinase C, and calcium in VEGF-induced venular hyperpermeability

1999 ◽  
Vol 276 (2) ◽  
pp. H535-H542 ◽  
Author(s):  
H. mac Wu ◽  
Yuan Yuan ◽  
David C. Zawieja ◽  
John Tinsley ◽  
Harris J. Granger
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Umbilical Vein ◽  
No Synthase ◽  
Serine Phosphorylation ◽  
No Production ◽  
Vegf Receptor ◽  
Apparent Permeability ◽  
Kinase C

We previously demonstrated that vascular endothelial growth factor (VEGF)-elicited increase in the permeability of coronary venules was blocked by the nitric oxide (NO) synthase inhibitor N G-monomethyl-l-arginine (l-NMMA). The aim of this study was to delineate in more detail the signaling pathways upstream from NO production in VEGF-induced venular hyperpermeability. The apparent permeability coefficient of albumin ( P a) and endothelial cytosolic Ca2+concentration ([Ca2+]i) were measured in intact perfused porcine coronary venules using fluorescence microscopy. VEGF (10−10 M) induced a two- to threefold increase in P a, which was blocked by a monoclonal antibody directed against the VEGF receptor Flk-1/KDR, the phospholipase C (PLC) antagonist U-73122, or the protein kinase C (PKC) antagonist bisindolylmaleimide (BIM). In 12 venules that displayed the [Ca2+]iresponse to bradykinin (10−6M) and ionomycin (10−6 M), only 4 vessels responded to VEGF with a transient increase in [Ca2+]i. Furthermore, Western blot analysis of cultured human umbilical vein endothelial cells showed that VEGF increased tyrosine phosphorylation of PLC-γ and serine phosphorylation of endothelial constitutive NO synthase (ecNOS). The hyperphosphorylation of PLC-γ was greatly attenuated by the KDR receptor antibody and U-73122, but not by BIM orl-NMMA. In contrast, U-73122 and BIM were able to inhibit VEGF-elicited serine phosphorylation of ecNOS. The results suggest that VEGF induces venular hyperpermeability through a KDR receptor-mediated activation of PLC. In turn, ecNOS is activated by PLC-mediated PKC and/or cytosolic Ca2+ elevation stimulation.

scholarly journals Tyrosine phosphorylation is involved in receptor coupling to phospholipase D but not phospholipase C in the human neutrophil

1992 ◽  
Vol 281 (3) ◽  
pp. 597-600 ◽  
Author(s):  
I J Uings ◽  
N T Thompson ◽  
R W Randall ◽  
G D Spacey ◽  
R W Bonser ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
Phospholipase D ◽  
Human Neutrophil ◽  
Human Neutrophils ◽  
Receptor Coupling ◽  
Kinase C

The tyrosine kinase inhibitors ST271, ST638 and erbstatin inhibited phospholipase D (PLD) activity in human neutrophils stimulated by fMet-Leu-Phe, platelet-activating factor and leukotriene B4. These compounds did not inhibit phorbol ester-stimulated PLD, indicating that they do not inhibit PLD per se, but probably act at a site between the receptor and the phospholipase. In contrast, the protein kinase C inhibitor Ro-31-8220 inhibited phorbol 12,13-dibutyrate- but not fMet-Leu-Phe-stimulated PLD activity, arguing against the involvement of protein kinase C in the receptor-mediated activation of PLD. ST271 did not inhibit Ins(1,4,5)P3 generation, but did inhibit protein tyrosine phosphorylation stimulated by fMet-Leu-Phe. The phosphotyrosine phosphatase inhibitor pervanadate increased tyrosine phosphorylation and stimulated PLD. These results suggest that tyrosine kinase activity is involved in receptor coupling to PLD but not to PtdIns(4,5)P2-specific phospholipase C in the human neutrophil.

scholarly journals Ethanol inhibits thrombin-induced secretion by human platelets at a site distinct from phospholipase C or protein kinase C

1990 ◽  
Vol 269 (2) ◽  
pp. 489-497 ◽  
Author(s):  
C Benistant ◽  
R Rubin
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Phorbol Ester ◽  
Inositol Phosphates ◽  
Shape Change ◽  
Protein A ◽  
Human Platelets ◽  
Kinase C ◽  
A Site

Ethanol is known to inhibit the activation of platelets in response to several physiological agonists, but the mechanism of this action is unclear. The addition of physiologically relevant concentrations of ethanol (25-150 mM) to suspensions of washed human platelets resulted in the inhibition of thrombin-induced secretion of 5-hydroxy[14C]tryptamine. Indomethacin was included in the incubation buffer to prevent feedback amplification by arachidonic acid metabolites. Ethanol had no effect on the activation of phospholipase C by thrombin, as determined by the formation of inositol phosphates and the mobilization of intracellular Ca2+. Moreover, ethanol did not interfere with the thrombin-induced formation of diacylglycerol or phosphatidic acid. Stimulation of platelets with phorbol ester (5-50 nM) resulted in 5-hydroxy[14C]tryptamine release comparable with those with threshold doses of thrombin. However, ethanol did not inhibit phorbol-ester-induced secretion. Ethanol also did not interfere with thrombin- or phorbol-ester-induced phosphorylation of myosin light chain (20 kDa) or a 47 kDa protein, a known substrate for protein kinase C. By electron microscopy, ethanol had no effect on thrombin-induced shape change and pseudopod formation, but prevented granule centralization and fusion. The results indicate that ethanol does not inhibit platelet secretion by interfering with the activation of phosphoinositide-specific phospholipase C or protein kinase C by thrombin. Rather, the data demonstrate an inhibition of a Ca2(+)-mediated event such as granule centralization.

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