Fig. 4: Inhibition of PTPN2 is associated with copper stimulated activation of EGFR. | Nature Communications

Fig. 4: Inhibition of PTPN2 is associated with copper stimulated activation of EGFR.

From: PTPN2 copper-sensing relays copper level fluctuations into EGFR/CREB activation and associated CTR1 transcriptional repression

Fig. 4

a Evaluation of the effects on EGR1 expression levels of 200 μM CuCl2 (60 min treatment) following siRNA knockdown of various PTPs in A549 cells. Depicted are two interpretations of the results. (top) All fold-changes are reported relative to the negative control siRNA transfect (Neg.) without CuCl2 supplementation. (bottom) Each result is reported as the fold-change between the denoted siRNA knockdown after 60 min 200 μM CuCl2 supplementation and the siRNA knockdown by itself. (n = 3 replicates per condition). Same box plot definitions as in Fig. 1. * denotes p < 0.05, ** denotes p < 0.01, and *** denotes p < 0.001 for two-sided t-test comparison between conditions. b pNPP (p-nitrophenyl phosphate) assay of ΔPTPN1 PTP activity following addition of various amounts of Cu1+ (n = 12 replicates per condition). c Proteome profiler antibody array volcano plot depicting statistically significant increases in phosphorylation levels following HEK 293 T supplementation with 20 μM ZnCl2. (n = 2 replicates for each condition). d Changes in A549 EGR1 expression levels 60 min after ZnCl2 supplementation. The fold-changes are overlayed on the fold-changes induced by CuCl2 supplementation for reference. (n = 2 replicates per condition). Same box plot definitions as in Fig. 1. e RNA-qPCR fold-changes of select transcripts 4 h post-supplementation of 500 nM CuGTSM or 5 µM CS1 relative to DMSO treated A549 cells. (n = 3 replicates per condition). Data points correspond to biological replicates, p-values calculated as paired two-tailed t-test. Same box plot definitions as in Fig. 1. Figure 4a, b, d, and e source data are provided as a Source Data file, as are exact p-values for Fig. 4a, e. * denotes p < 0.05, ** denotes p < 0.01, and *** denotes p < 0.001 for two-sided t-test comparison between conditions.

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