The carboxy-terminus of the human ARPKD protein fibrocystin can control STAT3 signalling by regulating SRC-activation.
cilia
genetic kidney diseases
polycystic kidney disease
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
15
06
2020
revised:
02
10
2020
accepted:
03
10
2020
pubmed:
29
10
2020
medline:
15
5
2021
entrez:
28
10
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33112055
doi: 10.1111/jcmm.16014
pmc: PMC7754027
doi:
Substances chimiques
PKHD1 protein, human
0
Receptors, Cell Surface
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
src-Family Kinases
EC 2.7.10.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14633-14638Subventions
Organisme : NIH HHS
ID : DK62338
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK062338
Pays : United States
Organisme : NIH HHS
ID : DK109563
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK109563
Pays : United States
Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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