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Phosphotyrosine enrichment identifies focal adhesion kinase and other tyrosine kinases for targeting in canine hemangiosarcoma
Author(s) -
Marley K.,
Maier C. S.,
Helfand S. C.
Publication year - 2012
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/j.1476-5829.2012.00325.x
Subject(s) - focal adhesion , ptk2 , autophosphorylation , receptor tyrosine kinase , tyrosine kinase , proto oncogene tyrosine protein kinase src , lyn , microbiology and biotechnology , cancer research , fyn , bruton's tyrosine kinase , chemistry , tyrosine phosphorylation , tyrosine , tyrosine protein kinase csk , phosphorylation , signal transduction , biology , sh2 domain , biochemistry , protein kinase a , mitogen activated protein kinase kinase
Canine hemangiosarcoma ( HSA ) is an endothelial cell malignancy driven, in part, by activating mutations in receptor and non‐receptor tyrosine kinases. Proteomics, Western blots and a tyrosine kinase inhibitor were used to elucidate activating mechanisms in HSA cell lines. Phosphotyrosine peptides from focal adhesion kinase ( FAK ) STAT 3, Lyn , Fyn and other signal transduction kinases were identified by mass spectrometry. FAK was constitutively activated at tyrosine 397, the autophosphorylation site, and this was reversible with high concentrations of a FAK inhibitor. FAK inhibitor‐14 suppressed migration and phosphorylation of FAK tyrosine 397 and tyrosines 576/577 and was cytotoxic to HSA cells suggesting FAK signalling may be an important contributor to canine HSA survival.