1. The carboxy‐terminus of the human ARPKD protein fibrocystin can control STAT3 signalling by regulating SRC‐activation
- Author
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Max C. Liebau, Antonio Mastrangelo, Heike Göbel, Thomas Benzing, Bernhard Schermer, Kathrin Burgmaier, Alina Braun, Claudia Dafinger, Amrei M. Mandel, Jörg Dötsch, Thomas Weimbs, and Laura Massella
- Subjects
STAT3 Transcription Factor ,0301 basic medicine ,Short Communication ,Short Communications ,Fibrocystin ,Receptors, Cell Surface ,urologic and male genital diseases ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Polycystic kidney disease ,medicine ,Humans ,Protein Interaction Domains and Motifs ,Phosphorylation ,STAT3 ,Polycystic Kidney, Autosomal Recessive ,polycystic kidney disease ,biology ,Chemistry ,Kinase ,Cilium ,cilia ,Cell Biology ,medicine.disease ,Immunohistochemistry ,Transmembrane protein ,Cell biology ,src-Family Kinases ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,STAT protein ,Molecular Medicine ,Signal Transduction ,genetic kidney diseases ,Proto-oncogene tyrosine-protein kinase Src - 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.
- Published
- 2020