LPS-Induced NF-κB Activation and TNF-α Release in Human Monocytes Are Protein Tyrosine Kinase Dependent and Protein Kinase C Independent

1999 ◽  
Vol 83 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Brian D. Shames ◽  
Craig H. Selzman ◽  
Edward J. Pulido ◽  
Xianzhong Meng ◽  
Daniel R. Meldrum ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Human Monocytes ◽  
Protein Tyrosine ◽  
Kinase C ◽  
Tnf Α

Platelet P-selectin expression: requirement for protein kinase C, but not protein tyrosine kinase or phosphoinositide 3-kinase

2003 ◽  
Vol 89 (06) ◽  
pp. 1016-1023 ◽  
Author(s):  
Danielle Libersan ◽  
Yahye Merhi
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Human Platelet ◽  
The Novel ◽  
Protein Tyrosine ◽  
Kinase C ◽  
Activated Platelets ◽  
Phosphoinositide 3 Kinase

SummaryP-selectin is translocated from the α-granules to the surface of activated platelets where it participates in thrombosis and inflammation. We investigated the signaling pathways involved in thrombin-induced human platelet P-selectin expression. Assessed by flow cytometry, inhibition of protein kinase C (PKC) with chelerythrine reduced P-selectin expression by 66%, platelet/neutrophil binding, GPIIb/IIIa activation and aggregation (p<0.05). Gö 6976, an inhibitor of the conventional PKCs (α and β), did not alter P-selectin expression. However, rottlerin inhibited by 50% its expression (p<0.05), but only at doses that interfere with the novel (є, η) and atypical (ζ) PKCs. Inhibition of protein tyrosine kinase (PTK) and phosphoinositide 3-kinase (PI3-K) did not significantly affect P-selectin expression. In conclusion, thrombin-induced P-selectin expression is PKC-sensitive, but PTK and PI3-K-insensitive. The novel є and η and atypical ζ, but not the conventional α and β and the novel θ PKCs, may be involved in this process.

Endothelin-1–Induced Interleukin-8 Production in Human Brain-Derived Endothelial Cells Is Mediated by the Protein Kinase C and Protein Tyrosine Kinase Pathways

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1291-1299 ◽  
Author(s):  
R. Zidovetzki ◽  
P. Chen ◽  
M. Chen ◽  
F.M. Hofman
Keyword(s):  
Signal Transduction ◽  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Protein Tyrosine ◽  
Kinase C ◽  
Eta Receptor ◽  
Specific Inhibitors

We have previously demonstrated that endothelin-1 (Et-1) induces human central nervous system-derived endothelial cells (CNS-EC) to produce and secrete the chemokine interleukin 8 (IL-8). In the present study, we use specific inhibitors and activators to elucidate the signal transduction pathways involved in this process. Et-1–induced IL-8 production was blocked by ETA receptor antagonist BQ610, but not by ETB receptor antagonist BQ788, demonstrating that CNS-EC activation is initiated by Et-1 binding to the ETA receptor. IL-8 mRNA expression is blocked by the protein kinase C inhibitor bisindolylmaleimide or protein tyrosine kinase inhibitors, genestein and geldanamycin, establishing the involvement of the protein kinase C and protein tyrosine kinase pathways in the activation process. The transcription factor, NF-κB, is involved in Et-1 activation as determined by specific inhibitors of translocation and direct analysis of DNA-binding proteins. Neither inhibition nor activation of cAMP-dependent protein kinase affected IL-8 production in the absence or presence of Et-1. Similarly, no effect was observed upon inhibition of protein phosphatases by okadaic acid. Thus, the signal transduction process induced by Et-1 in CNS-EC, leading to increased mRNA IL-8 expression, is initiated by Et-1 binding to ETA receptor followed by subsequent activation of protein kinase C, protein tyrosine kinase, and NF-κB. Because increased expression of Et-1 is associated with hypertension and stroke and IL-8 is likely to be involved in the accumulation of neutrophils causing tissue damage in ischemic/reperfusion injury, identification of the mechanism involved in the Et-1–induced increase in IL-8 production may have significant therapeutic value.

Endothelin-1–Induced Interleukin-8 Production in Human Brain-Derived Endothelial Cells Is Mediated by the Protein Kinase C and Protein Tyrosine Kinase Pathways

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1291-1299 ◽  
Author(s):  
R. Zidovetzki ◽  
P. Chen ◽  
M. Chen ◽  
F.M. Hofman
Keyword(s):  
Signal Transduction ◽  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Protein Tyrosine ◽  
Kinase C ◽  
Eta Receptor ◽  
Specific Inhibitors

Abstract We have previously demonstrated that endothelin-1 (Et-1) induces human central nervous system-derived endothelial cells (CNS-EC) to produce and secrete the chemokine interleukin 8 (IL-8). In the present study, we use specific inhibitors and activators to elucidate the signal transduction pathways involved in this process. Et-1–induced IL-8 production was blocked by ETA receptor antagonist BQ610, but not by ETB receptor antagonist BQ788, demonstrating that CNS-EC activation is initiated by Et-1 binding to the ETA receptor. IL-8 mRNA expression is blocked by the protein kinase C inhibitor bisindolylmaleimide or protein tyrosine kinase inhibitors, genestein and geldanamycin, establishing the involvement of the protein kinase C and protein tyrosine kinase pathways in the activation process. The transcription factor, NF-κB, is involved in Et-1 activation as determined by specific inhibitors of translocation and direct analysis of DNA-binding proteins. Neither inhibition nor activation of cAMP-dependent protein kinase affected IL-8 production in the absence or presence of Et-1. Similarly, no effect was observed upon inhibition of protein phosphatases by okadaic acid. Thus, the signal transduction process induced by Et-1 in CNS-EC, leading to increased mRNA IL-8 expression, is initiated by Et-1 binding to ETA receptor followed by subsequent activation of protein kinase C, protein tyrosine kinase, and NF-κB. Because increased expression of Et-1 is associated with hypertension and stroke and IL-8 is likely to be involved in the accumulation of neutrophils causing tissue damage in ischemic/reperfusion injury, identification of the mechanism involved in the Et-1–induced increase in IL-8 production may have significant therapeutic value.

Canine pulmonary vasoreactivity to serotonin: role of protein kinase C and tyrosine kinase

1997 ◽  
Vol 272 (2) ◽  
pp. H740-H747 ◽  
Author(s):  
S. A. Barman ◽  
J. R. Pauly ◽  
C. M. Isales
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Vascular Response ◽  
Protein Tyrosine ◽  
Kinase C ◽  
Voltage Dependent

The role of protein kinase C- and protein tyrosine kinase-mediated signal transduction in the canine pulmonary vascular response to serotonin (5-HT) was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. 5-HT (10(-5) M) significantly increased precapillary resistance by approximately 150% and postcapillary resistance twofold and significantly decreased total vascular compliance to approximately 50% of control values by decreasing large-vessel compliance and middle-compartment compliance. The 5-HT2-receptor blocker ketanserin (10(-7) M), the protein kinase C inhibitor staurosporine (10(-7) M), the voltage-dependent Ca2+-channel blocker verapamil (10(-5) M), and the specific protein tyrosine kinase inhibitors genistein (5 x 10(-4) M) and tyrphostin 25 (5 x 10(-4) M) completely inhibited the pressor response to 5-HT, whereas the 5-HT1-receptor antagonist (-)pindolol (10(-7) M) had no significant effect on the serotonergic response. These results indicate that the canine pulmonary vascular response to 5-HT involves activation of 5-HT2 receptors and suggests that this receptor signal transduction pathway involves protein kinase C and tyrosine kinase and the activation of voltage-dependent Ca2+ channels.

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