TY  - JOUR
A1  - Bürger, Claudia
A1  - Nagel-Wolfrum, Kerstin
A1  - Kunz, Christian
A1  - Wittig, Ilka
A1  - Butz, Karin
A1  - Hoppe-Seyler, Felix
A1  - Groner, Bernd
T1  - Sequence-specific peptide aptamers, interacting with the intracellular domain of the epidermal growth factor receptor, interfere with Stat3 activation and inhibit the growth of tumor cells
T2  - Journal of biological chemistry
N2  - Receptor tyrosine kinases of the epidermal growth factor (EGF) receptor family regulate essential cellular functions such as proliferation, survival, migration, and differentiation but also play central roles in the etiology and progression of tumors. We have identified short peptide sequences from a random peptide library integrated into the thioredoxin scaffold protein, which specifically bind to the intracellular domain of the EGF receptor (EGFR). These molecules have the potential to selectively inhibit specific aspects of EGF receptor signaling and might become valuable as anticancer agents. Intracellular expression of the aptamer encoding gene construct KDI1 or introduction of bacterially expressed KDI1 via a protein transduction domain into EGFR-expressing cells results in KDI1·EGF receptor complex formation, a slower proliferation, and reduced soft agar colony formation. Aptamer KDI1 did not summarily block the EGF receptor tyrosine kinase activity but selectively interfered with the EGF-induced phosphorylation of the tyrosine residues 845, 1068, and 1148 as well as the phosphorylation of tyrosine 317 of p46 Shc. EGF-induced phosphorylation of Stat3 at tyrosine 705 and Stat3-dependent transactivation were also impaired. Transduction of a short synthetic peptide aptamer sequence not embedded into the scaffold protein resulted in the same impairment of EGF-induced Stat3 activation.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76101
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-761015
SN  - 0021-9258
VL  - 278.2003
IS  - 39
SP  - 37610
EP  - 37621
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -