The Inhibitory Mechanisms of the Tyrosine Kinase Inhibitors Herbimycin A, Genistein, and Tyrphostin B48 with Regard to the Function of the Aryl Hydrocarbon Receptor in Caco-2 Cells

2010 ◽  
Vol 74 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Shuya KASAI ◽  
Hideaki KIKUCHI
Keyword(s):  
Tyrosine Kinase ◽  
Aryl Hydrocarbon Receptor ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Aryl Hydrocarbon ◽  
Herbimycin A ◽  
Inhibitory Mechanisms

Tyrosine kinase inhibitors block the glucocorticoid stimulation of prostaglandin endoperoxide H synthase expression in amnion cells

1999 ◽  
Vol 77 (2) ◽  
pp. 138-142 ◽  
Author(s):  
Tamas Zakar ◽  
Jane E Mijovic ◽  
Damyanti Bhardwaj ◽  
David M Olson
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Prostaglandin Endoperoxide ◽  
Herbimycin A ◽  
Cell Extracts ◽  
Endoperoxide H Synthase ◽  
Stimulation Of

Human amnion cells in primary culture respond to glucocorticoids in a characteristic fashion by the increased expression of the inducible prostaglandin endoperoxide H synthase isoenzyme, PGHS-2. Since PGHS-2 induction by agonists generally involves tyrosine kinases, we examined the possibility that the glucocorticoid stimulation of PGHS-2 in the amnion cells is tyrosine kinase dependent. PGHS-2 expression was stimulated in confluent, serum-starved amnion cells with dexamethasone, and the effect of the tyrosine kinase inhibitors herbimycin A and tyrphostins AG126, AG1288, and A1 on enzyme activity induction was determined. All four inhibitors blocked the increase of PGHS activity in a concentration-dependent manner with IC50 values of 0.077 ± 0.05, 15.38 ± 5.14, 20.91 ± 3.1, and 29.77 ± 8.21 µM, respectively (mean ± SE, n = 4). Dexamethasone increased (approximately twofold) the tyrosine phosphorylation of 120-, 110-, and 77-kDa proteins in cell extracts, and herbimycin A selectively blocked the phosphorylation of the 110-kDa phosphoprotein. The stimulation of the steady-state level of PGHS-2 mRNA by dexamethasone was also inhibited by herbimycin A. These results suggest that glucocorticoids induce PGHS-2 expression in amnion cells with the involvement of tyrosine kinase(s). The role of tyrosine kinase dependent mechanisms in the control of amnion cell responsiveness to corticosteroids remains to be established.Key words: amnion, glucocorticoid, tyrosine kinase, prostaglandin H synthase.

scholarly journals Integrin function: molecular hierarchies of cytoskeletal and signaling molecules.

1995 ◽  
Vol 131 (3) ◽  
pp. 791-805 ◽  
Author(s):  
S Miyamoto ◽  
H Teramoto ◽  
O A Coso ◽  
J S Gutkind ◽  
P D Burbelo ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Signaling Molecules ◽  
Cytochalasin D ◽  
Integrin Receptors ◽  
Jnk Pathway ◽  
Herbimycin A ◽  
Rapid Activation

Integrin receptors play important roles in organizing the actin-containing cytoskeleton and in signal transduction from the extracellular matrix. The initial steps in integrin function can be analyzed experimentally using beads coated with ligands or anti-integrin antibodies to trigger rapid focal transmembrane responses. A hierarchy of transmembrane actions was identified in this study. Simple integrin aggregation triggered localized transmembrane accumulation of 20 signal transduction molecules, including RhoA, Rac1, Ras, Raf, MEK, ERK, and JNK. In contrast, out of eight cytoskeletal molecules tested, only tensin coaccumulated. Integrin aggregation alone was also sufficient to induce rapid activation of the JNK pathway, with kinetics of activation different from those of ERK. The tyrosine kinase inhibitors herbimycin A or genistein blocked both the accumulation of 19 out of 20 signal transduction molecules and JNK- and ERK-mediated signaling. Cytochalasin D had identical effects, whereas three other tyrosine kinase inhibitors did not. The sole exception among signaling molecules was the kinase pp125FAK which continued to coaggregate with alpha 5 beta 1 integrins even in the presence of these inhibitors. Tyrosine kinase inhibition also failed to block the ability of ligand occupancy plus integrin aggregation to trigger transmembrane accumulation of the three cytoskeletal molecules talin, alpha-actinin, and vinculin; these molecules accumulated even in the presence of cytochalasin D. However, it was necessary to fulfill all four conditions, i.e., integrin aggregation, integrin occupancy, tyrosine kinase activity, and actin cytoskeletal integrity, to achieve integrin-mediated focal accumulation of other cytoskeletal molecules including F-actin and paxillin. Integrins therefore mediate a transmembrane hierarchy of molecular responses.

Side effects of tyrosine kinase inhibitors (TKIs) on bone remodelling

2012 ◽  
Vol 224 (03) ◽  
Author(s):  
JT Tauer ◽  
A Ulmer ◽  
LC Hofbauer ◽  
M Suttorp
Keyword(s):  
Side Effects ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Bone Remodelling

A framework for risk stratification in EGFR+ lung adenocarcinoma treated with tyrosine kinase inhibitors

2019 ◽  
Author(s):  
P Christopoulos ◽  
M Kirchner ◽  
F Bozorgmehr ◽  
N Magios ◽  
AL Volckmar ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors
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