FGF-21/FGF-21 receptor interaction and activation is determined by βKlotho

被引：294

作者：

Kharitonenkov, Alexei ^{[1
]}

Dunbar, James D. ^{[1
]}

Bina, Holly A. ^{[1
]}

Bright, Stuart ^{[1
]}

Moyers, Julie S. ^{[1
]}

Zhang, Chen ^{[1
]}

Ding, Liyun ^{[1
]}

Micanovic, Radmila ^{[1
]}

Mehrbod, Sean F. ^{[1
]}

Knierman, Michael D. ^{[1
]}

Hale, John E. ^{[1
]}

Coskun, Tamer ^{[1
]}

Shanafelt, Armen B. ^{[1
]}

机构：

[1] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2008年 / 215卷 / 01期

关键词：

D O I：

10.1002/jcp.21357

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 [细胞生物学]; 090102 [作物遗传育种];

摘要：

Fibroblast growth factor-21 (FGF-2 1) is a metabolic regulator that can influence glucose and lipid control in diabetic rodents and primates. We demonstrate that beta Klotho is an integral part of an activated FGF-21-beta Klotho-FGF receptor (FGFR) complex thus a critical subunit of the FGF-21 receptor. Cells lacking beta Klotho did not respond to FGF-21; the introduction of PKIotho to these cells conferred FGF-21-responsiveness and recapitulated the entire scope of FGF-21 signaling observed in naturally responsive cells. Interestingly, FGF-21-mediated effects are heparin independent suggesting that beta Klotho plays a role in FGF-21 activity similar to the one played by heparin in the signaling of conventional FGFs. Moreover, in addition to conferring specificity for FGF-2 1, beta Klotho appears to support FGF-19 activity and mediates the receptor selectivity profile of FGF-19. All together, these results indicate that beta Klothoand FGFRs form the cognate FGF-21 receptor complex, mediating FGF-21 cellular specificity and physiological effects.

引用

页码：1 / 7

页数：7

共 27 条

[1]

Badman MK, 2007, CELL METAB, V5, P426, DOI 10.1016/j.cmet.2007.05.002

[2]

The β-glucuronidase klotho hydrolyzes and activates the TRPV5 channel [J].

Chang, Q ;

Hoefs, S ;

van der Kemp, AW ;

Topala, CN ;

Bindels, RJ ;

Hoenderop, JG .

SCIENCE, 2005, 310 (5747) :490-493

[3]

Cellular signaling by fibroblast growth factor receptors [J].

Eswarakumar, VP ;

Lax, I ;

Schlessinger, J .

CYTOKINE & GROWTH FACTOR REVIEWS, 2005, 16 (02) :139-149

[4]

Fibroblast growth factor 19 increases metabolic rate I and reverses dietary and leptlin-deficient diabetes [J].

Fu, L ;

John, LM ;

Adams, SH ;

Yu, XX ;

Tomlinson, E ;

Renz, M ;

Williams, PM ;

Soriano, R ;

Corpuz, R ;

Moffat, B ;

Vandlen, R ;

Simmons, L ;

Foster, J ;

Stephan, JP ;

Tsai, SP ;

Stewart, TA .

ENDOCRINOLOGY, 2004, 145 (06) :2594-2603

[5]

Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members [J].

Goetz, Regina ;

Beenken, Andrew ;

Ibrahimi, Omar A. ;

Kalinina, Juliya ;

Olsen, Shaun K. ;

Eliseenkova, Anna V. ;

Xu, ChongFeng ;

Neubert, Thomas A. ;

Zhang, Fuming ;

Linhardt, Robert J. ;

Yu, Xijie ;

White, Kenneth E. ;

Inagaki, Takeshi ;

Kliewer, Steven A. ;

Yamamoto, Masaya ;

Kurosu, Hiroshi ;

Ogawa, Yasushi ;

Kuro-o, Makoto ;

Lanske, Beate ;

Razzaque, Mohammed S. ;

Mohammadi, Moosa .

MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (09) :3417-3428

[6]

Fibroblast growth factor signaling in tumorigenesis [J].

Grose, R ;

Dickson, C .

CYTOKINE & GROWTH FACTOR REVIEWS, 2005, 16 (02) :179-186

[7]

Forced expression of hepatocyte-specific fibroblast growth factor 21 delays initiation of chemically induced hepatocarcinogenesis [J].

Huang, Xinqiang ;

Yu, Chundong ;

Jin, Chengliu ;

Yang, Chaofeng ;

Xie, Rui ;

Cao, Dongdong ;

Wang, Fen ;

McKeehan, Wallace L. .

MOLECULAR CARCINOGENESIS, 2006, 45 (12) :934-942

[8]

Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis [J].

Inagaki, T ;

Choi, M ;

Moschetta, A ;

Peng, L ;

Cummins, CL ;

McDonald, JG ;

Luo, G ;

Jones, SA ;

Goodwin, B ;

Richardson, JA ;

Gerard, RD ;

Repa, JJ ;

Mangelsdorf, DJ ;

Kliewer, SA .

CELL METABOLISM, 2005, 2 (04) :217-225

[9]

Endocrine regulation of the fasting response by PPARα-mediated induction of fibroblast growth factor 21 [J].

Inagaki, Takeshi ;

Dutchak, Paul ;

Zhao, Guixiang ;

Ding, Xunshan ;

Gautron, Laurent ;

Parameswara, Vinay ;

Li, Yong ;

Goetz, Regina ;

Mohammadi, Moosa ;

Esser, Victoria ;

Elmquist, Joel K. ;

Gerard, Robert D. ;

Burgess, Shawn C. ;

Hammer, Robert E. ;

Mangelsdorf, David J. ;

Kliewer, Steven A. .

CELL METABOLISM, 2007, 5 (06) :415-425

[10]

Molecular cloning and expression analyses of mouse ßklotho, which encodes a novel Klotho family protein [J].

Ito, S ;

Kinoshita, S ;

Shiraishi, N ;

Nakagawa, S ;

Sekine, S ;

Fujimori, T ;

Nabeshima, Y .

MECHANISMS OF DEVELOPMENT, 2000, 98 (1-2) :115-119

← 1 2 3 →