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• W2895989767 abstract "The biological mechanisms underlying the effects of stem cell factor (SCF) and an inhibitor, NSC87877 (N) of the c-Kit negative regulator (SHP-1 and SHP-2) on cell proliferation are different. Therefore, we compared the cell's response to these two either alone or in combination in K562 cells. Binding of SCF (S) to c-Kit induces dimerization that activates its kinase activity. The activated c-Kit undergoes autophosphorylation at tyrosine residues that serve as a docking site for signal transduction molecules containing SH2 domains. Predominantly, the phosphotyrosine 568 (pY568) in Juxtamembrane (JM) region of c-Kit interacts with adaptor protein APS, Src family kinase, and SHP-2, while phosphotyrosine 570 (pY570) interacts with the SHP-1 and the adaptor protein Shc. The dephosphorylation of phosphotyrosine residues by SHP-1/SHP-2 leads to inhibition of c-Kit proliferative signaling. A chemical molecule, N is reported to inhibit the enzymatic activity of SHP-1/SHP-2, but its effect on c-Kit-mediated proliferation has not been studied yet. Thus, this work aims at examining the effect of the combination of S and N on cells growth as compared to individual treatment. The present study is performed with erythroleukemic K562 cells, chosen for its mRNA expression concerning the c-Kit, and SHP-1/SHP-2. Interestingly, proliferation assay showed that combination significantly increased proliferation when G1 sorted K562 cells were used. These changes were significantly higher when K562 cells were initially treated with N followed by S treatment. Collectively, these results give mechanistic insight into the proliferation enhancement of bone marrow transplantation through the synergistic effect of S and N by inhibiting SHP-1/SHP-2. The study gives solid evidence that S and N combination can be used to enhance cell proliferation/growth." @default.
• W2895989767 created "2018-10-26" @default.
• W2895989767 creator A5002142041 @default.
• W2895989767 creator A5004478158 @default.
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• W2895989767 date "2018-12-01" @default.
• W2895989767 modified "2023-09-27" @default.
• W2895989767 title "Stem cell factor and NSC87877 synergism enhances c-Kit mediated proliferation of human erythroid cells" @default.
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• W2895989767 doi "https://doi.org/10.1016/j.lfs.2018.09.055" @default.
• W2895989767 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30308182" @default.
• W2895989767 hasPublicationYear "2018" @default.
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