scholarly journals Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/neu in synovial sarcoma

Cancer ◽  
2005 ◽  
Vol 103 (4) ◽  
pp. 830-838 ◽  
Author(s):  
Dafydd G. Thomas ◽  
Thomas J. Giordano ◽  
Donita Sanders ◽  
Sybil Biermann ◽  
Vernon K. Sondak ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Synovial Sarcoma ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Her 2 ◽  
Epidermal Growth

scholarly journals Isatin-Hydrazones with Multiple Receptor Tyrosine Kinases (RTKs) Inhibitory Activity and In-Silico Binding Mechanism

2021 ◽  
Vol 11 (9) ◽  
pp. 3746
Author(s):  
Huda S. Al-Salem ◽  
Md Arifuzzaman ◽  
Iman S. Issa ◽  
A. F. M. Motiur Rahman
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Inhibitory Activity ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Competitive Inhibitors ◽  
Epidermal Growth ◽  
Multiple Receptor

Recently, we have reported a series of isatin hydrazone, two of them, namely, 3-((2,6-dichlorobenzylidene)hydrazono)indolin-2-one (1) and 3-((2-chloro-6-fluorobenzylidene)hydrazono)indolin-2-one (2) having potent cytotoxicity, showing cyclin-dependent kinases (CDK2) inhibitory activity and bearing recommended drug likeness properties. Since both compounds (1 and 2) showed inhibitory activity against CDK2, we assumed it would also have multiple receptor tyrosine kinases (RTKs) inhibitory activity. Considering those points, here, above-mentioned two isatin hydrazone 1 and 2 were synthesized using previously reported method for further investigation of their potency on RTKs (EGFR, VEGFR-2 and FLT-3) inhibitory activity. As expected, Compound 1 exhibited excellent inhibitory activity against epidermal growth factor receptor (EGFR, IC50 = 0.269 µM), vascular epidermal growth factor receptor 2 (VEGFR-2, IC50 = 0.232 µM) and FMS-like tyrosine kinase-3 (FLT-3, IC50 = 1.535 µM) tyrosine kinases. On the other hand, Compound 2 also exhibited excellent inhibitory activity against EGFR (IC50 = 0.369 µM), VEGFR-2 (IC50 = 0.266 µM) and FLT-3 (IC50 = 0.546 µM) tyrosine kinases. A molecular docking study with EGFR, VEGFR-2 and FLT-3 kinase suggested that both compounds act as type I ATP competitive inhibitors against EGFR and VEGFR-2, and type II ATP non-competitive inhibitors against FLT-3.

scholarly journals Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells.

1997 ◽  
Vol 8 (9) ◽  
pp. 1709-1721 ◽  
Author(s):  
H Y She ◽  
S Rockow ◽  
J Tang ◽  
R Nishimura ◽  
E Y Skolnik ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Adapter Protein ◽  
Src Homology ◽  
Epidermal Growth ◽  
Syndrome Protein

Src homology domains [i.e., Src homology domain 2 (SH2) and Src homology domain 3 (SH3)] play a critical role in linking receptor tyrosine kinases to downstream signaling networks. A well-defined function of the SH3-SH2-SH3 adapter Grb2 is to link receptor tyrosine kinases, such as the epidermal growth factor receptor (EGFR), to the p21ras-signaling pathway. Grb2 has also been implicated to play a role in growth factor-regulated actin assembly and receptor endocytosis, although the underlying mechanisms remain unclear. In this study, we show that Grb2 interacts through its SH3 domains with the human Wiskott-Aldrich syndrome protein (WASp), which plays a role in regulation of the actin cytoskeleton. We find that WASp is expressed in a variety of cell types and is exclusively cytoplasmic. Although the N-terminal SH3 domain of Grb2 binds significantly stronger than the C-terminal SH3 domain to WASp, full-length Grb2 shows the strongest binding. Both phosphorylation of WASp and its interaction with Grb2, as well as with another adapter protein Nck, remain constitutive in serum-starved or epidermal growth factor-stimulated cells. WASp coimmunoprecipitates with the activated EGFR after epidermal growth factor stimulation. Purified glutathione S-transferase-full-length-Grb2 fusion protein, but not the individual domains of Grb2, enhances the association of WASp with the EGFR, suggesting that Grb2 mediates the association of WASp with EGFR. This study suggests that Grb2 translocates WASp from the cytoplasm to the plasma membrane and the Grb2-WASp complex may play a role in linking receptor tyrosine kinases to the actin cytoskeleton.

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