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

ABSTRACT: Fluxes in human copper levels recently garnered attention for roles in cellular signaling, including affecting levels of the signaling molecule cyclic adenosine monophosphate. We herein apply an unbiased temporal evaluation of the signaling and whole genome transcriptional activities modulated by copper level fluctuations to identify potential copper sensor proteins responsible for driving these activities. We find that fluctuations in physiologically relevant copper levels modulate EGFR signal transduction and activation of the transcription factor CREB. Both intracellular and extracellular assays support Cu¹⁺ inhibition of the EGFR phosphatase PTPN2 (and potentially PTPN1)-via ligation to the PTPN2 active site cysteine side chain-as the underlying mechanism. We additionally sh

SUBMITTER: Ross MO 

PROVIDER: S-EPMC11322707 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature