Inhibition of epidermal growth factor‐induced DNA synthesis by tyrosine kinase inhibitors

Umezawa, Kazuo; Hori, Takashi; Tajima, Hiroto; Imoto, Masaya; Isshiki, Kunio; Takeuchi, Tomio

doi:10.1016/0014-5793(90)80102-o

Cited by 126 publications

(61 citation statements)

References 8 publications

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“…The present results are the first to show that the CPAinduced vasorelaxation, accompanied by increased cyclic GMP formation, was inhibited by methyl 2,5-dihydroxycinnamate, which has been reported to be a tyrosine kinase inhibitor (10). In rat thoracic aorta, it has been previously assumed by us (2) that CPA may act on the ER in endothelial cells to deplete Ca 2+ by inhibition of the Ca 2+-pumping ATPase, which then triggers the influx of extracellular Ca 21 in a similar way to that proposed in the capacitative Ca 2+ entry model for parotid acinar cells (3) and cultured endothelial cells (5).…”

supporting

confidence: 58%

Tyrosine Kinase May Participate in Ca2+ Entry for Endothelial Nitric Oxide Production

Hisayama

Kida

Imada

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-We have suggested that cyclopiazonic acid (CPA), a Ca 2+-ATPase inhibitor, produces nitric oxide (NO) by triggering a Ca2+-influx resulting from Ca 2+-depletion in the endoplasmic reticulum of endothelial cells. The tyrosine kinase inhibitor methyl 2,5-dihydroxycinnamate, while having no effect on relaxations induced by A23187 or Na nitroprusside, did inhibit the CPA-induced relaxation and cyclic GMP formation in rat aorta. Tyrosine kinase may participate in endothelial NO synthesis through activation of a Ca 2' entry mechanism.

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supporting

confidence: 58%

Tyrosine Kinase May Participate in Ca2+ Entry for Endothelial Nitric Oxide Production

Hisayama

Kida

Imada

et al. 1995

Japanese Journal of Pharmacology

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“…The inactive genistein analogue, daidzein (100 M), did not inhibit (not shown). Erbstatin analogue, a tyrosine kinase inhibitor not chemically related to genistein (18), also completely suppressed receptor-activation of TRPC3 (Fig. 1A).…”

Section: Resultsmentioning

confidence: 92%

Obligatory Role of Src Kinase in the Signaling Mechanism for TRPC3 Cation Channels

Vázquez

Wedel

Kawasaki

et al. 2004

Journal of Biological Chemistry

147

105

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Members of the canonical transient receptor potential (TRPC) subfamily of cation channels are candidates for capacitative and non-capacitative Ca 2؉ entry channels. When ectopically expressed in cell lines, TRPC3 can be activated by phospholipase C-mediated generation of diacylglycerol or by addition of synthetic diacylglycerols, independently of Ca 2؉ store depletion. Apart from this mode of regulation, little is known about other receptordependent signaling events that modulate TRPC3 activity. In the present study the role of tyrosine kinases in receptor-and diacylglycerol-dependent activation of TRPC3 was investigated. In HEK293 cells stably expressing TRPC3, pharmacological inhibition of tyrosine kinases, and specifically of Src kinases, abolished activation of TRPC3 by muscarinic receptor stimulation and by diacylglycerol. Channel regulation was lost following expression of a dominant-negative mutant of Src, or when TRPC3 was expressed in an Src-deficient cell line. In both instances, wild-type Src restored TRPC3 regulation. We conclude that Src plays an obligatory role in the mechanism for receptor and diacylglycerol activation of TRPC3.In many types of cells, membrane receptors coupled to phospholipase C (PLC) 1 promote inositol 1,4,5-trisphosphate (IP 3 )-mediated release of Ca 2ϩ from endoplasmic reticulum and Ca 2ϩ entry across the plasma membrane through both capacitative or store-operated and non-capacitative calcium entry pathways (1-3). Although the molecular identity of capacitative and noncapacitative calcium entry channels, as well as the signaling mechanisms involved, remain uncertain, mammalian homologues of the Drosophila melanogaster transient receptor potential (TRP) channel have been considered as potential candidates (4, 5), particularly members of the canonical TRP (TRPC) subfamily (designated TRPC1 through TRPC7 (6)). The human isoform of TRPC3, originally cloned by Zhu et al. (7), has been shown in many heterologous expression systems to behave as a receptoractivated channel that can be activated also by exogenous application of diacylglycerols (DAGs) independently of store depletion. In fact, DAG-induced activation of TRPC3 and its structural relatives TRPC6 and TRPC7 (8, 9) provides the likely mechanism of activation of these channels by phosphoinositide-specific PLClinked receptors, independently of IP 3 and store depletion. Apart from its regulation by DAG generated from PLC stimulation through either G-protein-coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs), little is known about additional signaling pathways downstream of receptor-stimulation involved in activation of TRPC3. Stimulation of either of these receptor pathways results in rapid tyrosine phosphorylation of cellular proteins (10, 11), and so in the present study we investigated whether tyrosine kinases might play a role in the signaling mechanism underlying receptor-and DAG-dependent activation of TRPC3. We found that inhibition of tyrosine kinase activity completely abrogated the ability of either GPCR st...

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“…Daidzein did not affect E-selectin expression induced by IL-la or TNFa at concentrations up to 100 pM (30 pg ml-1); however, 100 pM daidzein partially inhibited PMA-induced expression (24 + 6% inhibition, P<0.001). An additional tyrosine kinase inhibitor, methyl-2,5-dihydroxy-cinnamate (MDHC), which is a stable analogue of erbstatin (Umezawa et al, 1990) failed to inhibit IL-la-, TNFa-or PMA-induced E-selectin expression at concentrations up to 20 pM (data not shown). At concentrations exceeding 20 pM MDHC was cytotoxic.…”

Section: Discussionmentioning

confidence: 99%

Effects of protein tyrosine kinase inhibitors on cytokine‐induced adhesion molecule expression by human umbilical vein endothelial cells

May

Wheeler‐Jones

Pearson

1996

British J Pharmacology

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. Endothelial cells can be stimulated by the pro‐inflammatory cytokines interleukin (IL)‐1α and tumour necrosis factor (TNF)α to express the leukocyte adhesion molecules E‐selectin, vascular cell adhesion molecule (VCAM)‐1 and intercellular adhesion molecule (ICAM)‐1 but the intracellular signalling mechanisms leading to this expression are incompletely understood. We have investigated the role of protein tyrosine kinases (PTK) in adhesion molecule expression by cytokine‐activated human umbilical vein endothelial cells (HUVEC) using the PTK inhibitors genistein and herbimycin A, and the protein tyrosine phosphatase (PTP) inhibitor sodium orthovanadate. . Maximal E‐selectin expression induced by incubation of HUVEC for 4 h with IL‐1α (100 u ml−1) and TNFα (100 u ml−1) was dose‐dependently inhibited by genistein and herbimycin A. Although similar effects were seen on phorbol 12‐myristate, 13‐acetate (PMA)‐induced expression, this was not due to inhibition of protein kinase C (PKC) activity as the selective inhibitors of PKC, bisindolylmaleimide (BIM), Ro31‐7549 or Ro31‐8220 did not affect IL‐1α‐ or TNFα‐induced E‐selectin expression at concentrations which maximally inhibited PMA‐induced expression. . Genistein inhibited VCAM‐1 expression induced by incubation of HUVEC for 24 h with TNFα or IL‐1α whereas it did not affect ICAM‐1 expression induced by 24 h incubation with either of these cytokines. Herbimycin A inhibited both VCAM‐1 and ICAM‐1 expression induced by TNFα. . Basal expression of E‐selectin, VCAM‐1 and ICAM‐1 was dose‐dependently enhanced by sodium orthovanadate. In contrast, vanadate differentially affected TNFα‐induced expression of these molecules with maximal E‐selectin and ICAM‐1 expression being slightly enhanced and VCAM‐1 expression dose‐dependently reduced. . We also studied the effects of PTK and PTP inhibitors on adhesion of the human pre‐myeloid cell line U937 to TNFα‐stimulated HUVEC. Adhesion of U937 cells to HUVEC pretreated for 4 or 24 h with TNFα was dose‐dependently inhibited by genistein and herbimycin A but unaffected by daidzein. Adhesion of U937 cells after 4 h was partially inhibited by blocking antibodies against both E‐selectin and VCAM‐1 but after 24 h was only inhibited by anti‐VCAM‐1. . Sodium orthovanadate had no effect on TNFα‐induced U937 adhesion but dose‐dependently enhanced adhesion to unstimulated HUVEC. Vanadate‐induced adhesion was inhibited by an antibody against VCAM‐1. . These results demonstrate that PTK‐mediated phosphorylation events are important for the regulation of adhesion molecule expression by human endothelial cells, and additionally show that PTK inhibitors differentially affect upregulation of different adhesion molecules, implicating divergent regulatory pathways for cytokine‐induced adhesion molecule expression.

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Inhibition of epidermal growth factor‐induced DNA synthesis by tyrosine kinase inhibitors

Cited by 126 publications

References 8 publications

Tyrosine Kinase May Participate in Ca2+ Entry for Endothelial Nitric Oxide Production

Tyrosine Kinase May Participate in Ca2+ Entry for Endothelial Nitric Oxide Production

Obligatory Role of Src Kinase in the Signaling Mechanism for TRPC3 Cation Channels

Effects of protein tyrosine kinase inhibitors on cytokine‐induced adhesion molecule expression by human umbilical vein endothelial cells

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