Inhibition of protein kinase c by the tyrosine kinase inhibitor erbstatin

Bishop, W. Robert; Petrin, Joanne; Wang, Lynn; Ramesh, U.; Doll, Ronald J.

doi:10.1016/0006-2952(90)90245-g

Cited by 40 publications

(11 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, it has been demonstrated that besides inhibiting tyrosine kinases, genistein also antagonizes the thromboxane A 2 receptor on platelets (Nakashima et al, 1991;McNicol, 1993). In addition, erbstatin was found to directly inhibit protein kinase C besides tyrosine kinases (Bishop et al, 1990). In this study, we show that MNS is more potent than genistein in inhibiting agonist-induced protein tyrosine phosphorylation in platelets.…”

Section: Mns Inhibits Platelet Gpiib/iiia Activation 1387supporting

confidence: 54%

Prevention of Platelet Glycoprotein IIb/IIIa Activation by 3,4-Methylenedioxy-β-Nitrostyrene, A Novel Tyrosine Kinase Inhibitor

Wang

Wu²,

2006

Mol Pharmacol

113

View full text Add to dashboard Cite

Binding fibrinogen to activated glycoprotein (GP)IIb/IIIa is the final common pathway of platelet aggregation and has become a successful target for antiplatelet therapy. In the present study, we found that a small chemical compound, 3,4-methylenedioxy-␤-nitrostyrene (MNS), exhibited potent and broadspectrum inhibitory effects on human platelet aggregation caused by various stimulators. Moreover, addition of MNS to human platelets that had been aggregated by ADP caused a rapid disaggregation. We demonstrated that the antiaggregatory activity of MNS is due to inhibition of GPIIb/IIIa activation by measuring the binding amount of PAC-1 in platelets. In contrast, MNS is not a direct antagonist of GPIIb/IIIa, because MNS did not affect fibrinogen binding to fixed ADP-stimulated platelets. By investigating how MNS inhibits GPIIb/IIIa activation, we found that MNS potently inhibited the activity of tyrosine kinases (Src and Syk) and prevented protein tyrosine phosphorylation and cytoskeletal association of GPIIb/IIIa and talin, but it had no direct effects on protein kinase C, Ca 2ϩ mobilization, Ca 2ϩ -dependent enzymes (myosin light chain kinase and calpain), and arachidonic acid metabolism, and it did not affect the cellular levels of cyclic nucleotides. Therefore, MNS represents a new class of tyrosine kinase inhibitor that potently prevents GPIIb/IIIa activation and platelet aggregation without directly affecting other signaling pathways required for platelet activation. Because MNS inhibits GPIIb/IIIa functions in a manner different from GPIIb/IIIa antagonists, this feature may provide a new strategy for treatment of platelet-dependent thrombosis.

show abstract

Section: Mns Inhibits Platelet Gpiib/iiia Activation 1387supporting

confidence: 54%

Prevention of Platelet Glycoprotein IIb/IIIa Activation by 3,4-Methylenedioxy-β-Nitrostyrene, A Novel Tyrosine Kinase Inhibitor

Wang

Wu²,

2006

Mol Pharmacol

113

View full text Add to dashboard Cite

show abstract

“…It was also reported that erbstatin was competitive with respect to the peptide substrate and non-competitive with respect to ATP for the inhibition of EGFR PTK purified from A431 cells [65]. Further studies have shown that erbstatin is a relatively potent inhibitor of PKC (IC 50 = 19.5 µM) and similar potency was observed against other serine/threonine kinases [66].…”

Section: Iv21 Ptk Inhibitory Activity Of Styrenesmentioning

confidence: 84%

“…In addition, Lineweaver-Burk plotting with histone as a substrate showed that desmal competed with peptide substrate but not with ATP. It was rather unexpected since all very active flavonoids such as genistein (66) and orobol (68) inhibited PTK activity by competing with ATP [136]. A substrate-competitive inhibitor would be advantageous for specific inhibition of PTKs.…”

Section: Iv65 Flavanonesmentioning

confidence: 96%

Plant-Derived Protein Tyrosine Kinase Inhibitors as Anticancer Agents

Hollósy

Kéri

2004

CMCACA

View full text Add to dashboard Cite

Protein tyrosine kinases play a fundamental role in signal transduction pathways regulating a number of cellular functions such as cell growth, differentiation and cell death. Tyrosine kinases are, therefore attractive targets for the design of new therapeutic agents, not only against cancer, but also against many other diseases. Numerous tyrosine kinase inhibitors have been discovered by screening of plant extracts based on ethnopharmacological and chemotaxonomical knowledge. Specific screening approaches have led to the isolation of structurally distinct classes of inhibitors, including phenylpropanes, chalcones, flavonoids, coumarins, styrenes, quinones and terpenes. These natural inhibitors have served as valuable leads for further design and synthesis of more active analogues. Many of these inhibitors have also been used in probing the molecular and cellular mechanisms involved in the protein tyrosine kinase mediated signal transduction. In this review, plant-derived protein tyrosine kinase inhibitors and their synthetic analogues were systematically evaluated based on their plant origin, structure-activity relationship and anticancer efficacy.

show abstract

“…For example, genistein, a widely used tyrosine kinase inhibitor, inhibits (at concentrations similar to those used to inhibit tyrosine kinase) topoisomerase I and II, phosphatidylinositol turnover and histidine kinase (Okura et al, 1988;Imoto et al, 1988;Huang et al, 1992), by competing with these enzymes for adenosine 5'-triphosphate (ATP) (Akiyama et al, 1987). Erbstatin, another widely used tyrosine kinase inhibitor, has been shown to inhibit PKC with an IC50 of 19.8 + 3.2 gM (Bishop et al, 1990) by competing for ATP.…”

Section: Introductionmentioning

confidence: 99%

Tumour necrosis factor‐α‐induced ICAM‐1 expression in human vascular endothelial and lung epithelial cells: modulation by tyrosine kinase inhibitors

Burke‐Gaffney

Hellewell

1996

British J Pharmacology

View full text Add to dashboard Cite

Tumour necrosis factor‐α (TNFα) increases the expression of the adhesion molecule intercellular adhesion molecule‐1 (ICAM‐1) on cultured endothelial and epithelial cells and modulation of this may be important in controlling inflammation. Activation of tyrosine kinase(s) is known to be involved in the signal transduction pathways of many cytokines. In this study we have investigated the effects of the tyrosine kinase inhibitors, ST638, tyrphostin AG 1288 and genistein, on TNFα‐induced ICAM‐1 expression in human alveolar epithelial (A549) and vascular endothelial (EAhy926) cell lines and also normal human lung microvascular endothelial cells (HLMVEC). ICAM‐1 expression on cultured cells was determined by a sensitive enzyme‐linked immunosorbant assay (ELISA). Endothelial or epithelial monolayers were exposed to increasing doses of TNF‐α (0.01–10 ng ml−1), in the presence or absence of either ST638 (3–100 μm), AG 1288 (3–100 μm) or genistein (100 μm) and ICAM‐1 expression was measured at 4 and 24 h. Control experiments examined the effect of ST638 on phorbol 12‐myristate 13‐acetate (PMA, 20 ng ml−1, 4 h)‐stimulated ICAM‐1 and compared it to that of a specific protein kinase C inhibitor, Ro31‐8220 (10 μm). Also, functional consequences of changes in ICAM‐1 expression were assessed by measuring adhesion of 111In‐labelled human neutrophils to EAhy926 endothelial and A549 epithelial monolayers treated with TNFα, in the presence or absence of ST638. ST638 caused a concentration‐dependent reduction in TNFα‐ (0.1–10 ng ml−1‐induced ICAM‐1 on EAhy926 endothelial (at 4 h) and A549 epithelial monolayers (at 4 and 24 h). In contrast, ST638 caused a concentration‐dependent increase in TNFα‐ (0.1–10 ng ml−1‐induced ICAM‐1 on EAhy926 endothelial cells at 24 h. Similar effects were seen with AG 1288 or genistein. ST638 (100 μm) significantly (P < 0.01) inhibited ICAM‐1 expression on HLMVEC endothelial cells induced by 0.01 ng ml−1 TNFα at 4 or 24 h or 0.1 ng ml−1 at 4 h, but increased ICAM‐1 expression induced by 0.1 ng ml−1 TNFα at 24 h. ST638 did not significantly change the expression of PMA‐stimulated ICAM‐1 on either A549 epithelial, EAhy926 or HLMVEC endothelial cells. However, PMA‐induced ICAM‐1 expression was inhibited by Ro31‐8220. Also, treatment of epithelial or endothelial monolayers with TNFα and ST638 altered adhesion of human neutrophils to A549 epithelial or EAhy926 endothelial cells in a manner that corresponded to the alteration in ICAM‐1 expression. These results show that tyrosine kinase inhibitors alter TNFα‐induced ICAM‐1 expression, but that the cell type, concentration of TNFα and time of exposure to this cytokine determine whether expression is decreased or increased by the inhibitor. An increased understanding of the signal transduction pathway(s) involved in TNFα‐induced ICAM‐1 expression on lung epithelial and vascular endothelial cells may be of potential therapeutic value in the treatment of inflammatory disease.

show abstract

Inhibition of protein kinase c by the tyrosine kinase inhibitor erbstatin

Cited by 40 publications

References 33 publications

Prevention of Platelet Glycoprotein IIb/IIIa Activation by 3,4-Methylenedioxy-β-Nitrostyrene, A Novel Tyrosine Kinase Inhibitor

Prevention of Platelet Glycoprotein IIb/IIIa Activation by 3,4-Methylenedioxy-β-Nitrostyrene, A Novel Tyrosine Kinase Inhibitor

Plant-Derived Protein Tyrosine Kinase Inhibitors as Anticancer Agents

Tumour necrosis factor‐α‐induced ICAM‐1 expression in human vascular endothelial and lung epithelial cells: modulation by tyrosine kinase inhibitors

Contact Info

Product

Resources

About