Struktura i funkcje białka βKlotho

• Authors: Agnieszka Szymczak , Rafał Krzywański , Ewa Forma

Title variants

EN

The structure and functions of βKlotho protein

• Languages of publication: PL

Abstracts

PL

Gen βKlotho (KLB) odkryty został w roku 2000, jako homolog genu αKlotho. Gen KLB koduje monotopowe białko przezbłonowe, ulegające ekspresji głównie w wątrobie i białej tkance tłuszczowej. W odróżnieniu od myszy αKL–/–, myszy KLB–/– rozwijają się prawidłowo, jednakże wykazują one znaczny wzrost biosyntezy kwasów żółciowych oraz oporność na tworzenie się kamieni żółciowych. Podobny fenotyp obserwuje się również u myszy z wyłączonym genem FGFR4 lub FGF15. Dane te były podstawą sugestii, że białko βKlotho oddziałuje z FGFR4 i pełni rolę koreceptora dla FGF15. Dalsze analizy pokazały, że βKlotho tworzy również kompleks z receptorem FGFR1c, funkcjonując jako koreceptor dla czynnika FGF21. Wykazano, że poprzez działanie na szlaku FGF-FGFR, białko βKlotho zaangażowane jest w regulację licznych procesów komórkowych. Funkcjonując jako koreceptor dla czynnika FGF19 (ortolog FGF15 u człowieka), KLB wpływa m.in. na metabolizm kwasów żółciowych oraz homeostazę energetyczną. Natomiast jako koreceptor dla FGF21, białko KLB wpływa na promocję lipolizy w białek tkance tłuszczowej oraz ketogenezy w wątrobie.

EN

The βKlotho gene was identified on 2000, based on sequence similarity with the αKlotho gene. The KLB gene encoded single-pass transmembrane protein, which is expressed predominantly in liver and white adipose tissue. KLB–/–mice, unlike αKL–/– mice, grow and develop quite normally, but they exhibit increased bile acid synthesis and resistance to gallstone formation. Similar phenotype was also observed in mice lacking FGFR4 or FGF15. These observations led to hypothesis, that βKlotho interacts with FGFR4 and functions as a coreceptor for FGF15. Subsequent studies have shown, that βKlotho form complex with FGFR1c and function as coreceptor for FGF21. It was found, that via FGF-FGFR signalling pathway βKlotho can regulate many cellular processes. Functions as coreceptor for FGF19 (the orthologous protein in humans), KLB can regulate inter alia bile acids metabolism and energy homeostasis. Function as coreceptor for FGF21 protein can mediate promotion of lypolisis in white adipose tissue and ketogenesis in liver.

Keywords

EN

FGF15/19; FGF21; metabolism; metabolizm; βKlotho

Discipline

• MEDICINE: MEDICINE

• Publisher: Łódzkie Towarzystwo Naukowe
• Journal: Folia Medica Lodziensia
• Year: 2013
• Volume: 40
• Issue: 1
• Pages: 99-132

Contributors

author

Agnieszka Szymczak

• Katedra Cytobiochemii, Wydział Biologii i Ochrony Środowiska, Uniwersytet Łódzki

author

Rafał Krzywański

• Katedra Cytobiochemii, Wydział Biologii i Ochrony Środowiska, Uniwersytet Łódzki

author

Ewa Forma

• Katedra Cytobiochemii, Wydział Biologii i Ochrony Środowiska, Uniwersytet Łódzki

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• Document Type: paper