5.47 Tyrosine Kinase Inhibitor, Gefitinib, is Cytotoxic Against Zeta-Chain-Associated Protein Kinase 70-Positive but not Zeta-Chain-Associated Protein Kinase 70-Negative CLL Cells

2011 ◽  
Vol 11 ◽  
pp. S276
Author(s):  
Wenyan Xiao ◽  
Ju Yoon Yoon ◽  
Edward Noh ◽  
Michelle Brown ◽  
James B. Johnston ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Zeta Chain

scholarly journals Transforming growth factor-α increases tyrosine phosphorylation of microtubule-associated protein kinase in a small intestinal crypt cell line (IEC-6)

1994 ◽  
Vol 303 (2) ◽  
pp. 455-460 ◽  
Author(s):  
B L Oliver ◽  
R I Sha'afi ◽  
J J Hajjar
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Phosphorylation ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
Intestinal Crypt ◽  
Small Intestinal ◽  
Intestinal Crypt Cell

The small intestinal crypt cell line (IEC-6) is an undifferentiated, untransformed, mitotically active cell used in this study to determine the effect of transforming growth factor-alpha (TGF-alpha) on tyrosine phosphorylation levels of cellular proteins. Thymidine incorporation increased maximally after addition of 2 ng/ml TGF-alpha for 24 h. At the same dose, TGF-alpha induced the tyrosine phosphorylation of proteins with approximate molecular masses of 42, 44, 52, 80, 150 and 175 kDa as shown by Western blots treated with anti-phosphotyrosine antibody. The most intense phosphorylation was seen in the 42 kDa (p42) and 44 kDa (p44) proteins, which were identified as two isoforms of microtubule-associated protein kinase (MAPK). This phosphorylation was seen as early as 5 min post stimulation and was dose dependent. Both p42 and p44 were found in the nucleus after stimulation, although a basal level of unphosphorylated protein was present before stimulation. The observed tyrosine phosphorylation of p42 and p44 was inhibited by genistein, a tyrosine kinase inhibitor, and tyrphostin 23, an epidermal growth factor receptor tyrosine kinase inhibitor. We conclude that MAPK is tyrosine phosphorylated in response to TGF-alpha stimulation of IEC-6 cells.

cAMP-independent activation of CFTR Cl channels by the tyrosine kinase inhibitor genistein

1995 ◽  
Vol 268 (4) ◽  
pp. C886-C893 ◽  
Author(s):  
B. Illek ◽  
H. Fischer ◽  
G. F. Santos ◽  
J. H. Widdicombe ◽  
T. E. Machen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Protein Kinase A ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Anion Channel ◽  
3T3 Fibroblasts ◽  
Nih 3T3 ◽  
Kinase A

Genistein, a protein tyrosine kinase inhibitor, activates the cystic fibrosis transmembrane conductance regulator (CFTR) in transfected NIH-3T3 fibroblasts that express the CFTR (3T3-CFTR). CFTR activity was assayed by 125I efflux and by patch clamping in the cell-attached mode. Both forskolin and genistein stimulated 125I efflux and activated a 9-10 pS anion channel in 3T3-CFTR cells but failed to activate 125I efflux in mock-transfected NIH-3T3 cells. Genistein, unlike forskolin and 3-isobutyl-1-methylxanthine, did not increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP) above control levels. This demonstrates that genistein-dependent activation does not involve inhibition of phosphodiesterase activity and suggests that stimulation does not involve a direct activation of protein kinase A. Genistein stimulated 125I efflux to approximately 50% of the maximal rate with forskolin. Genistein did not increase 125I efflux at saturating forskolin but decreased the concentration of forskolin required for half-maximal stimulation. Orthovanadate (VO4), a phosphotyrosine phosphatase inhibitor, inhibited genistein-induced channel activation with an inhibition constant of approximately 20 microM. These effects suggest that, in addition to activation by protein kinase A, the CFTR is regulated by a tyrosine kinase-dependent pathway.

Inhibition of protein kinase c by the tyrosine kinase inhibitor erbstatin

1990 ◽  
Vol 40 (9) ◽  
pp. 2129-2135 ◽  
Author(s):  
W.Robert Bishop ◽  
Joanne Petrin ◽  
Lynn Wang ◽  
Usha Ramesh ◽  
Ronald J. Doll
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Kinase C
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