Role of protein kinase C and tyrosine kinase activity in IFN-gamma-induced expression of the class II MHC gene

1995 ◽  
Vol 268 (1) ◽  
pp. C127-C137 ◽  
Author(s):  
Y. J. Lee ◽  
R. B. Panek ◽  
M. Huston ◽  
E. N. Benveniste
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Class Ii ◽  
Factor X ◽  
Induced Expression ◽  
Ifn Gamma ◽  
Kinase C ◽  
Class Ii Mhc

Astrocytes are induced by interferon-gamma (IFN-gamma) to express class II major histocompatibility complex (MHC) antigens. Our previous studies demonstrated that IFN-gamma-initiated signaling events important for class II expression include activation of protein kinase C (PKC) and the Na+/H+ antiporter. We have extended these studies and found that protein tyrosine kinase (PTK) activity is also required for class II expression. Treatment of astrocytes with inhibitors specific for PKC and PTK blocked INF-gamma-induced class II gene transcription, mRNA expression, and protein expression. Immunoblotting and immunoprecipitation experiments demonstrated that IFN-gamma induced tyrosine phosphorylation of the p91 component of ISGF3, which is blocked by preincubation of cells with PTK inhibitors. Treatment of astrocytes with IFN-gamma and either PKC and PTK inhibitors changed the mobility and intensity of a nuclear factor, IFN-gamma-enhanced factor X, which binds to the X box of the class II MHC promoter. Taken together, these data provide evidence that activation of both PTK and PKC is required for IFN-gamma-induced expression of the class II gene.

HLA class-II-mediated homotypic aggregation: Involvement of a protein tyrosine kinase and protein kinase C

1992 ◽  
Vol 34 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Rafael Ramirez ◽  
Julia Carracedo ◽  
Nuala Mooney ◽  
Dominique Charron
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Class Ii ◽  
Hla Class Ii ◽  
Protein Tyrosine ◽  
Kinase C

Phosphorylation of class I but not class II MHC molecules by membrane-localized protein kinase C

1989 ◽  
Vol 26 (12) ◽  
pp. 1095-1104 ◽  
Author(s):  
Teresa Burke ◽  
Karen Pollok ◽  
William Cushley ◽  
E. Charles Snow
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Class Ii ◽  
Class I ◽  
Mhc Molecules ◽  
Kinase C ◽  
Class Ii Mhc

scholarly journals The expression of COX-2 in VEGF-treated endothelial cells is mediated through protein tyrosine kinase

2002 ◽  
Vol 11 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Pravit Akarasereenont ◽  
Kitirat Techatraisak ◽  
Athiwat Thaworn ◽  
Sirikul Chotewuttakorn
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Kinase C ◽  
Protein Kinase C Inhibitor ◽  
Cox 2 ◽  
Cox 1

Cyclooxygenase (COX), existing as the COX-1 and COX-2 isoforms, converts arachidonic acid to prostaglandin H2, which is then further metabolized to various prostaglandins. Vascular endothelial growth factor (VEGF) has been shown to play important roles in inflammation and is upregulated by the prostaglandin E series through COX-2 in several cell types. Here, we have investigated the effects of VEGF on the COX isoform expressed in human umbilical vein endothelial cells (HUVEC). The signalling mechanism of the COX isoform expressed in endothelial cells activated with VEGF will be also investigated using the tyrosine kinase inhibitor, genistein, and protein kinase C inhibitor, staurosporine. The activity of COX2 was assessed by measuring the production of 6-keto-prostaglandin F1α in the presence of exogenous arachidonic acids (10 μM, 10 min) by enzyme immunoassay. The expression of COX isoform protein was detected by immunoblot using specific antibodies. Untreated HUVEC contained no COX-2 protein. In HUVEC treated with VEGF (0.01-50 ng/ml), COX-2 protein, but not COX-1, and COX activity were increased in a dose-dependent manner. Interestingly, the increased COX-2 protein and activity in response to VEGF (10 ng/ml) was inhibited by the tyrosine kinase inhibitor, genistein (0.05-5 μg/ml), but not by the protein kinase C inhibitor, staurosporine (0.1-10 ng/ml). Thus, the induction of COX-2 by VEGF in endothelial cells was mediated through protein tyrosine kinase, and the uses of specific COX-2 inhibitors in these conditions, in which VEGF was involved, might have a role.

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.

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