Lessons from (S)-6-(1-(6-(1-Methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline (PF-04254644), an Inhibitor of Receptor Tyrosine Kinase c-Met with High Protein Kinase Selectivity but Broad Phosphodiesterase Family Inhibition Leading to Myocardial Degeneration in Rats

2013 ◽  
Vol 56 (17) ◽  
pp. 6651-6665 ◽  
Author(s):  
J. Jean Cui ◽  
Hong Shen ◽  
Michelle Tran-Dubé ◽  
Mitchell Nambu ◽  
Michele McTigue ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
High Protein ◽  
Kinase C ◽  
Myocardial Degeneration

Prevention by Protein Kinase C Inhibitors of Glucose-Induced Insulin-Receptor Tyrosine Kinase Resistance in Rat Fat Cells

Diabetes ◽  
1991 ◽  
Vol 40 (11) ◽  
pp. 1440-1448 ◽  
Author(s):  
H. K. Muller ◽  
M. Kellerer ◽  
B. Ermel ◽  
A. Muhlhofer ◽  
B. Obermaier-Kusser ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Receptor Tyrosine Kinase ◽  
Fat Cells ◽  
Insulin Receptor Tyrosine Kinase ◽  
Protein Kinase C Inhibitors ◽  
Kinase C ◽  
Rat Fat Cells

scholarly journals Signalling-competent truncated forms of ErbB2 in breast cancer cells: differential regulation by protein kinase C and phosphatidylinositol 3-kinase

1999 ◽  
Vol 344 (2) ◽  
pp. 339-348 ◽  
Author(s):  
Azucena ESPARÍS-OGANDO ◽  
Elena DÍAZ-RODRÍGUEZ ◽  
Atanasio PANDIELLA
Keyword(s):  
Breast Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Receptor Tyrosine Kinase ◽  
Breast Cancer Cells ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase C ◽  
Phosphatidylinositol 3

Alterations that affect the ectodomain of receptor tyrosine kinases are often associated with constitutive activation of the enzymic activity of the mutant cell-associated receptor. Since the ectodomain of the ErbB2 receptor tyrosine kinase has been detected as a soluble fragment in the culture supernatant of cells and serum from patients with advanced breast cancer, the possible presence of cell-associated truncated forms of ErbB2 in cancer cells was investigated. Several cell-bound N-terminal truncated forms of ErbB2 were identified in breast cancer cells overexpressing this receptor. The presence of the truncated fragments was independent of lysosomal/proteasomal activity, indicating that classical receptor tyrosine kinase degradation systems were not involved in the N-terminal cleavages. The presence of these truncated forms of ErbB2 was up-regulated by protein kinase C and neuregulin; and down-regulated by phosphatidylinositol 3-kinase, and monoclonal antibodies that target the ectodomain of ErbB2, indicating that N-terminal cleavages of ErbB2 were regulated by multiple mechanisms. The truncated fragments were tyrosine-phosphorylated under resting conditions, and associated with the signalling intermediates Shc and Grb2. It is therefore likely that these truncated forms may be endowed with constitutive activity that allows them to permanently signal.

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