Percorrer por autor "Cortopassi, Gino"
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- Impact of SHC-1 adaptor protein inhibitors on the plasma membrane abundance of the CFTR channel in epithelial cellsPublication . Barros, Patrícia; Pereira, Mariana F.L.; Tomilev, Alexey; Cortopassi, Gino; Jordan, Peter; Matos, PauloCFTR is a chloride and bicarbonate channel essential for ionic homeostasis in epithelial cells, and its plasma membrane (PM) abundance is often downregulated in chronic obstructive pulmonary disease (COPD) and colon cancer (CRC). CFTR endocytosis is promoted by Y512 phosphorylation by spleen tyrosine kinase, mediated by SHC-1, a phospho-tyrosine adaptor in MAPK signaling. Since the drug idebenone (IDE) disrupts SHC-1/phospho-insulin receptor interaction in hepatocytes, we tested its effects on CFTR internalization. In CFBE airway cells, IDE and a novel SHC-1 inhibitor (110#3) increased CFTR PM levels but also elevated PM levels of GLUT1 and E-cadherin, indicating a MAPK signaling-independent, non-specific action. Moreover, neither compound affected CFTR PM abundance or MAPK activity in 16HBE airway or Caco-2 intestinal cells. These findings underscore the context-dependent nature of SHC-1 signaling, suggesting IDE and related compounds may not universally disrupt SHC-1 interactions, or specifically block CFTR internalization in the airway or CRC cells.