Impact of protein tyrosine kinase 6 (PTK6) on human epidermal growth factor receptor (HER) signalling in breast cancer

2011 ◽  
Vol 7 (5) ◽  
pp. 1603 ◽  
Author(s):  
Natalie Ludyga ◽  
Nataša Anastasov ◽  
Iria Gonzalez-Vasconcellos ◽  
Manuela Ram ◽  
Heinz Höfler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Protein Tyrosine ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

Salicylanilides as Inhibitors of the Protein Tyrosine Kinase Epidermal Growth Factor Receptor.

ChemInform ◽  
2004 ◽  
Vol 35 (29) ◽  
Author(s):  
Christoph Liechti ◽  
Urs Sequin ◽  
Guido Bold ◽  
Pascal Furet ◽  
Thomas Meyer ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Protein Tyrosine ◽  
Epidermal Growth

scholarly journals Trastuzumab Blocks the Receiver Function of HER2 Leading to the Population Shifts of HER2-Containing Homodimers and Heterodimers

Antibodies ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 7
Author(s):  
Jun Zhao ◽  
Nishant Mohan ◽  
Ruth Nussinov ◽  
Buyong Ma ◽  
Wen Jin Wu
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Tyrosine Kinase Domain ◽  
Her Family ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

HER2, a member of the Erythroblastosis Protein B/Human Epidermal Growth Factor Receptor (ErbB/HER) family of receptor tyrosine kinase, is overexpressed in 20~30% of human breast cancers. Trastuzumab, a HER2-targeted therapeutic monoclonal antibody, was developed to interfere with the homodimerization of HER2 in HER2-overexpressing breast cancer cells, which attenuates HER2-mediated signaling. Trastuzumab binds to the domain IV of the HER2 extracellular domain and does not directly block the dimerization interface of HER2-HER2 molecules. The three-dimensional structures of the tyrosine kinase domains of ErbB/HER family receptors show asymmetrical packing of the two monomers with distinct conformations. One monomer functions as an activator, whereas the other acts as a receiver. Once activated, the receiver monomer phosphorylates the activator or other proteins. Interestingly, in our previous work, we found that the binding of trastuzumab induced phosphorylation of HER2 with the phosphorylation pattern of HER2 that is different from that mediated by epidermal growth factor (EGF) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Binding of trastuzumab to HER2 promoted an allosteric effect of HER2, in both tyrosine kinase domain and ectodomain of HER2 although details of allosteric regulation were missing. In this study, we utilized molecular dynamics (MD) simulations to model the allosteric consequences of trastuzumab binding to HER2 homodimers and heterodimers, along with the apo forms as controls. We focused on the conformational changes of HER2 in its monomeric and dimeric forms. The data indicated the apparent dual role of trastuzumab as an antagonist and an agonist. The molecular details of the simulation provide an atomic level description and molecular insight into the action of HER2-targeted antibody therapeutics.

Aggregation-induced activation of the epidermal growth factor receptor protein tyrosine kinase

Biochemistry ◽  
1993 ◽  
Vol 32 (34) ◽  
pp. 8742-8748 ◽  
Author(s):  
Moosa Mohammadi ◽  
Annemarie Honegger ◽  
Andrey Sorokin ◽  
Axel Ullrich ◽  
Joseph Schlessinger ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Receptor Protein ◽  
Protein Tyrosine ◽  
Epidermal Growth ◽  
Receptor Protein Tyrosine Kinase
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