scholarly journals Activation of phospholipase A2 and stimulation of prostaglandin E2 production by transforming growth factor-α in rat thymic epithelial cells requires influx of calcium

1993 ◽  
Vol 293 (1) ◽  
pp. 109-113 ◽  
Author(s):  
P Liu ◽  
M Wen ◽  
L Sun ◽  
J Hayashi
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Enzymic Activity ◽  
Pge2 Production ◽  
Thymic Epithelial Cells ◽  
Factor I ◽  
Stimulation Of

The stimulation of both phospholipase A2 (PLA2) enzymic activity and the production of prostaglandin E2 (PGE2) by transforming growth factor-alpha (TGF-alpha) and Ca2+ ionophore A23187 in TEA3A1 rat thymic epithelial cells were studied. TGF-alpha by itself at various concentrations (5-200 ng/ml) had no effect on the stimulation of PGE2 production. A23187 (1 microgram/ml) by itself stimulated PGE2 production on average by 18-fold over the control. When TGF-alpha (50 ng/ml) was added to the cells in the presence of A23187, a synergistic stimulation (on average 45-fold) of PGE2 production was observed. Synergistic stimulation was also observed at the level of arachidonic acid released from phospholipid pools, suggesting the activation of PLA2 enzymic activity. We have found that this synergistic activation of PLA2 enzymic activity and subsequent stimulation of PGE2 production required the activation of epidermal growth factor (EGF) receptor tyrosine kinase and Ca2+ influx. This was shown by the fact that genistein, an inhibitor of tyrosine kinase, blocks the synergistic stimulation by TGF-alpha and A23187 and by the fact that the stimulation of PGE2 production by TGF-alpha and A23187 is dependent on the culture-medium Ca2+ concentrations. The requirement for Ca2+ influx instead of intracellular mobilization of Ca2+ was shown by the fact that PGE2 production was not stimulated when cells were treated with TGF-alpha and thapsigargin. Moreover, the synergistic stimulation of PGE2 production by TGF-alpha and A23187 was not affected in protein kinase C down-modulated cells. In addition, the synergistic stimulation was not observed in cells treated with either phorbol 12-myristate 13-acetate (PMA) and TGF-alpha or PMA and A23187, and in cells treated with TGF-alpha and thapsigargin. The requirement for the activation of receptor tyrosine kinase seems to be specific to the EGF receptor, since a synergistic stimulation of PGE2 production was not observed when cells are treated with either insulin-like growth factor-I or fibroblast growth factor-I in the presence of A23187.

scholarly journals Insulin-like growth factor I in cultured rat astrocytes: expression of the gene, and receptor tyrosine kinase.

1987 ◽  
Vol 6 (12) ◽  
pp. 3633-3639 ◽  
Author(s):  
R. Ballotti ◽  
F. C. Nielsen ◽  
N. Pringle ◽  
A. Kowalski ◽  
W. D. Richardson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Rat Astrocytes ◽  
Growth Factor I

scholarly journals Rapid uptake of tyrphostin into A431 human epidermoid cells is followed by delayed inhibition of epidermal growth factor (EGF)-stimulated EGF receptor tyrosine kinase activity.

1991 ◽  
Vol 11 (5) ◽  
pp. 2697-2703 ◽  
Author(s):  
C A Faaland ◽  
F H Mermelstein ◽  
J Hayashi ◽  
J D Laskin
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Kinase Activity ◽  
Egf Receptor ◽  
Tyrosine Kinase Activity ◽  
A431 Cells ◽  
Epidermal Growth

Treatment of A431 human epidermoid cells with epidermal growth factor (EGF; 20 nM) results in decreased proliferation. This is associated with blockage of the cells in the S and/or G2 phases of the cell cycle. We found that tyrphostin, a putative tyrosine kinase inhibitor, in the range of 50 to 100 microM, partially reversed the growth-inhibitory and cell cycle changes induced by EGF. By using high-pressure liquid chromatography with electrochemical detection, we found that tyrphostin was readily incorporated into A431 cells, reaching maximal levels within 1 h. Although tyrphostin (50 to 100 microM) had no effect on high-affinity binding of EGF to its receptor in A431 cells for up to 24 h, the compound partially inhibited EGF-stimulated EGF receptor tyrosine kinase activity. However, this effect was evident only after prolonged treatment of the cells (4 to 24 h) with the drug. When the peak intracellular concentration of tyrphostin occurred (1 h), no inhibition of tyrosine kinase activity was observed. After both 1 and 24 h, tyrphostin was a less effective inhibitor of tyrosine kinase activity than the potent tumor promoter 12-O-tetradecanoyl phorbol-13-acetate, which almost completely blocked EGF receptor autophosphorylation. On the basis of our data, we hypothesize that tyrphostin is not a competitive inhibitor of the EGF receptor tyrosine kinase in intact cells and that it functions by an indirect mechanism.

Insulin-and insulin-like growth-factor-I receptor tyrosine-kinase activities in human renal carcinoma

1995 ◽  
Vol 62 (5) ◽  
pp. 501-507 ◽  
Author(s):  
Monika Kellerer ◽  
Helena von Eye Corleta ◽  
Andreas Mühlhöfer ◽  
Edison Capp ◽  
Luitgard Mosthaf ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Renal Carcinoma ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I ◽  
Human Renal Carcinoma

scholarly journals Characterization of ATP receptor responsible for the activation of phospholipase A2 and stimulation of prostaglandin E2 production in thymic epithelial cells

1995 ◽  
Vol 308 (2) ◽  
pp. 399-404 ◽  
Author(s):  
P Liu ◽  
M Wen ◽  
J Hayashi
Keyword(s):  
Epithelial Cells ◽  
Prostaglandin E2 ◽  
Phospholipase A2 ◽  
Enzymic Activity ◽  
Pge2 Production ◽  
Thymic Epithelial Cells ◽  
Cross Linking ◽  
Atp Binding ◽  
Variant Cell ◽  
Stimulation Of

In TEA3A1 rat thymic epithelial cells, ATP stimulates prostaglandin E2 (PGE2) production through activation of phospholipase A2 (PLA2) enzymic activity. The stimulation of PGE2 production tested with other nucleotides indicated the agonist potency of adenosine 5′-[gamma-thio]triphosphate (ATP[S]) > or = UTP > ATP, with ED50 of about 10 microM for ATP[S]. In TEA3A1 cells, cross-linking studies with ATP[35S] revealed the presence of four cell-surface cross-linked bands of 42 kDa, 53 kDa, 83 kDa and 100 kDa in Triton X-100 extracts of TEA3A1 cells by fluorography. Guanosine 5′-[gamma-thio]triphosphate specifically blocked the cross-linking of ATP[35S] to the 53 kDa, 83 kDa and 100 kDa ATP-binding proteins, and inhibited the ATP[S]-mediated stimulation of PGE2 production with an ED50 of about 25 microM. On the other hand, 2-methylthioadenosine triphosphate (2MeSATP) blocked ATP[35S] cross-linking to the 42 kDa protein, but had no effect on ATP[S]-mediated stimulation of PGE2 production. In a variant cell line, TEAvarl, derived from TEA3A1 cells that lost their response to ATP in the activation of PLA2, the presence of 83 kDa ATP-binding protein was not detected. Results from our study suggest that ATP activates PLA2 enzymic activity in TEA3A1 cells by binding to an atypical ATP receptor that has not been described previously.

scholarly journals Liver Kinase B1 Expression Promotes Phosphatase Activity and Abrogation of Receptor Tyrosine Kinase Phosphorylation in Human Cancer Cells

2013 ◽  
Vol 289 (3) ◽  
pp. 1639-1648 ◽  
Author(s):  
Imoh S. Okon ◽  
Kathleen A. Coughlan ◽  
Ming-Hui Zou
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Receptor Tyrosine Kinase ◽  
Egf Receptor ◽  
Liver Kinase B1 ◽  
Kinase Phosphorylation

Aberrant receptor tyrosine kinase phosphorylation (pRTK) has been associated with diverse pathological conditions, including human neoplasms. In lung cancer, frequent liver kinase B1 (LKB1) mutations correlate with tumor progression, but potential links with pRTK remain unknown. Heightened and sustained receptor activation was demonstrated by LKB1-deficient A549 (lung) and HeLaS3 (cervical) cancer cell lines. Depletion (siRNA) of endogenous LKB1 expression in H1792 lung cancer cells also correlated with increased pRTK. However, ectopic LKB1 expression in A549 and HeLaS3 cell lines, as well as H1975 activating-EGF receptor mutant lung cancer cell resulted in dephosphorylation of several tumor-enhancing RTKs, including EGF receptor, ErbB2, hepatocyte growth factor receptor (c-Met), EphA2, rearranged during transfection (RET), and insulin-like growth factor I receptor. Receptor abrogation correlated with attenuation of phospho-Akt and increased apoptosis. Global phosphatase inhibition by orthovanadate or depletion of protein tyrosine phosphatases (PTPs) resulted in the recovery of receptor phosphorylation. Specifically, the activity of SHP-2, PTP-1β, and PTP-PEST was enhanced by LKB1-expressing cells. Our findings provide novel insight on how LKB1 loss of expression or function promotes aberrant RTK signaling and rapid growth of cancer cells.

Erythrocyte insulin and insulin-like growth factor-I receptor tyrosine kinase activity in hypertension in pregnancy

Metabolism ◽  
1995 ◽  
Vol 44 (10) ◽  
pp. 1308-1313 ◽  
Author(s):  
James R. Sowers ◽  
David B. Jacobs ◽  
Lori Simpson ◽  
Bassam Al-Homsi ◽  
George Grunberger ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Kinase Activity ◽  
Insulin Like Growth Factor ◽  
Tyrosine Kinase Activity ◽  
Factor I ◽  
Hypertension In Pregnancy ◽  
Growth Factor I ◽  
In Pregnancy
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