@article{oai:repo.qst.go.jp:00045996,
 author = {Saito, Yuriko and Furukawa, Takako and Arano, Yasushi and Fujibayashi, Yasuhisa and Saga, Tsuneo and 齋藤 有里子 and 古川 高子 and 荒野 泰 and 藤林 康久 and 佐賀 恒夫},
 issue = {2},
 journal = {International Journal of Oncology},
 month = {Jun},
 note = {Epidermal growth factor receptor (EGFR) and other receptor tyrosine kinases (RTKs) are overexpressed and/or mutated in various cancers and their abnormal activation
is implicated in carcinogenesis. We explored the possibility of generating an imaging probe for RTK activation using the SH2 domain of Grb2 for cancer characterization. For cell penetration, molecular analysis and radiolabeling, the SH2 domain was fused with TAT, flag and tyrosine residue, respectively (termed TSF). We analyzed TSF characteristics in cells such as cellular uptake, stability and localization.
After uptake into EGFR-expressing cells, TSF was found to be binding to phosphorylated-EGFR, which increased by stimulation with EGF. TSF was co-localized with EGFR in EGFR-activated cells, while it was localized as dots in cytosol in EGFR-non-activated cells. Cellular retention time of TSF was significantly extended under EGFR activation with EGF stimuli and reduced under the treatment with a tyrosine kinase inhibitor, Tyrphostin AG1478. In conclusion, the SH2 domain of Grb2 has the potential to be used as a binding component of a probe to detect activated-RTK and to evaluate the effect of kinase inhibitors on RTK activation.},
 pages = {281--287},
 title = {Basic study on SH2 domain of Grb2 as a molecular probe for detection of RTK activation},
 volume = {37},
 year = {2010}
}