RRC ID 44736
Author Saka K, Kawahara M, Nagamune T.
Title Quantitative control of intracellular signaling activity through chimeric receptors incorporating multiple identical tyrosine motifs.
Journal Biotechnol Bioeng
Abstract Controlling activation levels and durations of native signaling molecules is important for efficiently controlling cellular fates. Previously we developed single-chain Fv (scFv)/cytokine receptor chimeras incorporating tyrosine motifs in the intracellular domain, which artificially control the activation of specific intracellular signaling proteins. In this study, to quantitatively control the activation levels of signaling molecules with an extended dynamic range, we constructed scFv/receptor chimeras incorporating multiple identical motifs at the different positions in the intracellular domain. We used retroviral transduction to express chimeric receptors with multiple STAT3 binding motifs connected with or without flexible linkers in a murine IL-3-dependent pro-B cell line, Ba/F3. Our results showed that the chimeric receptors can control the activation levels of STAT3 depending on ligand concentration and the number of motifs. The existence of linkers between the motifs also affected the signal intensity. Furthermore, the STAT3 activation levels significantly depended on the number of motifs rather than the distance from the JAK-binding region to the tyrosine motif.
Volume 111(5)
Pages 948-55
Published 2014-5
DOI 10.1002/bit.25151
PMID 24222636
MeSH Animals Binding Sites / genetics Cell Line Mice Recombinant Fusion Proteins / chemistry Recombinant Fusion Proteins / genetics* Recombinant Fusion Proteins / metabolism STAT3 Transcription Factor Signal Transduction / genetics* Single-Chain Antibodies / chemistry Single-Chain Antibodies / genetics* Single-Chain Antibodies / metabolism Tyrosine / chemistry Tyrosine / genetics* Tyrosine / metabolism
IF 4.26
Times Cited 2
Human and Animal Cells