The carboxy-terminus of the human ARPKD protein fibrocystin can control STAT3 signalling by regulating SRC-activation

Claudia Dafinger, Amrei M. Mandel, Alina Braun, Heike Göbel, Kathrin Burgmaier, Laura Massella, Antonio Mastrangelo, Jörg Dötsch, Thomas Benzing, Thomas Weimbs, Bernhard Schermer, Max C. Liebau

Research output: Contribution to journalArticlepeer-review

Abstract

Autosomal recessive polycystic kidney disease (ARPKD) is mainly caused by variants in the PKHD1 gene, encoding fibrocystin (FC), a large transmembrane protein of incompletely understood cellular function. Here, we show that a C-terminal fragment of human FC can suppress a signalling module of the kinase SRC and signal transducer and activator of transcription 3 (STAT3). Consistently, we identified truncating genetic variants specifically affecting the cytoplasmic tail in ARPKD patients, found SRC and the cytoplasmic tail of fibrocystin in a joint dynamic protein complex and observed increased activation of both SRC and STAT3 in cyst-lining renal epithelial cells of ARPKD patients.

Original languageEnglish
Pages (from-to)14633-14638
Number of pages6
JournalJournal of Cellular and Molecular Medicine
Volume24
Issue number24
DOIs
Publication statusPublished - Dec 2020

Keywords

  • cilia
  • genetic kidney diseases
  • polycystic kidney disease

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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