GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:18187602

From GONUTS
Jump to: navigation, search
Citation

Suzuki, M, Uehara, Y, Motomura-Matsuzaka, K, Oki, J, Koyama, Y, Kimura, M, Asada, M, Komi-Kuramochi, A, Oka, S and Imamura, T (2008) betaKlotho is required for fibroblast growth factor (FGF) 21 signaling through FGF receptor (FGFR) 1c and FGFR3c. Mol. Endocrinol. 22:1006-14

Abstract

Fibroblast growth factor (FGF) 21, a structural relative of FGF23 that regulates phosphate homeostasis, is a regulator of insulin-independent glucose transport in adipocytes and plays a role in the regulation of body weight. It also regulates ketogenesis and adaptive responses to starvation. We report that in a reconstituted receptor activation assay system using BaF3 cells, which do not endogenously express any type of FGF receptor (FGFR) or heparan sulfate proteoglycan, FGF21 alone does not activate FGFRs and that betaKlotho is required for FGF21 to activate two specific FGFR subtypes: FGFR1c and FGFR3c. Coexpression of betaKlotho and FGFR1c on BaF3 cells enabled FGF21, but not FGF23, to activate receptor signaling. Conversely, coexpression of FGFR1c and Klotho, a protein related to betaKlotho, enabled FGF23 but not FGF21 to activate receptor signaling, indicating that expression of betaKlotho/Klotho confers target cell specificity on FGF21/FGF23. In all of these cases, heparin enhanced the activation but was not essential. In 3T3-L1 adipocytes, up-regulation of glucose transporter (GLUT) expression by FGF21 was associated with expression of betaKlotho, which was absent in undifferentiated 3T3-L1 fibroblasts. It is thus suggested that betaKlotho expression is a crucial determinant of the FGF21 specificity of the target cells upon which it acts in an endocrine fashion.

Links

PubMed Online version:10.1210/me.2007-0313

Keywords

3T3-L1 Cells; Animals; Fibroblast Growth Factors/pharmacology; Gene Expression/drug effects; Glucose Transport Proteins, Facilitative/genetics; Glucose Transport Proteins, Facilitative/metabolism; Glucuronidase/genetics; Glucuronidase/metabolism; Immunoblotting; Mice; Protein Binding; RNA, Messenger/genetics; RNA, Messenger/metabolism; Receptor, Fibroblast Growth Factor, Type 1/genetics; Receptor, Fibroblast Growth Factor, Type 1/metabolism; Receptor, Fibroblast Growth Factor, Type 3/genetics; Receptor, Fibroblast Growth Factor, Type 3/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FGFR1

acts_upstream_of_or_within

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1861377
MGI:MGI:1932466
UniProtKB:O95750
UniProtKB:P05230

P

Seeded From UniProt

complete

MOUSE:FGFR1

acts_upstream_of_or_within

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1861377
MGI:MGI:1932466
UniProtKB:O95750
UniProtKB:P05230

P

Seeded From UniProt

complete

MOUSE:FGFR1

acts_upstream_of_or_within

GO:0090080: positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1861377
MGI:MGI:1932466

P

Seeded From UniProt

complete

MOUSE:FGFR3

acts_upstream_of_or_within

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1861377
MGI:MGI:1932466
UniProtKB:O95750
UniProtKB:P05230

P

Seeded From UniProt

complete

MOUSE:FGFR3

acts_upstream_of_or_within

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1861377
MGI:MGI:1932466
UniProtKB:O95750
UniProtKB:P05230

P

Seeded From UniProt

complete

MOUSE:FGFR3

acts_upstream_of_or_within

GO:0090080: positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1861377
MGI:MGI:1932466

P

Seeded From UniProt

complete

MOUSE:KLOTB

acts_upstream_of_or_within

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1861377
MGI:MGI:95522
MGI:MGI:95524

P

Seeded From UniProt

complete

MOUSE:KLOTB

acts_upstream_of_or_within

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1861377
MGI:MGI:95522
MGI:MGI:95524

P

Seeded From UniProt

complete

MOUSE:KLOTB

acts_upstream_of_or_within

GO:0090080: positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1861377
MGI:MGI:95522
MGI:MGI:95524

P

Seeded From UniProt

complete

HUMAN:FGF1

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q61851

P

Seeded From UniProt

complete

HUMAN:FGF1

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q03142

P

Seeded From UniProt

complete

HUMAN:FGF1

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P21803

P

Seeded From UniProt

complete

HUMAN:FGF1

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P16092

P

Seeded From UniProt

complete

HUMAN:FGF1

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q61851

P

Seeded From UniProt

complete

HUMAN:FGF1

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q03142

P

Seeded From UniProt

complete

HUMAN:FGF1

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P21803

P

Seeded From UniProt

complete

HUMAN:FGF1

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P16092

P

Seeded From UniProt

complete

HUMAN:FGF19

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q03142

P

Seeded From UniProt

complete

HUMAN:FGF19

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q61851

P

Seeded From UniProt

complete

HUMAN:FGF19

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P21803

P

Seeded From UniProt

complete

HUMAN:FGF19

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P16092

P

Seeded From UniProt

complete

HUMAN:FGF19

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q61851

P

Seeded From UniProt

complete

HUMAN:FGF19

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q03142

P

Seeded From UniProt

complete

HUMAN:FGF19

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P16092

P

Seeded From UniProt

complete

HUMAN:FGF19

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P21803

P

Seeded From UniProt

complete

MOUSE:FGF21

acts_upstream_of_or_within

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1932466
MGI:MGI:95522
MGI:MGI:95524

P

Seeded From UniProt

complete

MOUSE:FGF21

acts_upstream_of_or_within

GO:0090080: positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1932466
MGI:MGI:95522
MGI:MGI:95524

P

Seeded From UniProt

complete

MOUSE:FGFR2

acts_upstream_of_or_within

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:O95750
UniProtKB:P05230

P

Seeded From UniProt

complete

MOUSE:FGFR2

acts_upstream_of_or_within

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:O95750
UniProtKB:P05230

P

Seeded From UniProt

complete

MOUSE:FGFR4

acts_upstream_of_or_within

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:O95750
UniProtKB:P05230

P

Seeded From UniProt

complete

MOUSE:FGFR4

acts_upstream_of_or_within

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:O95750
UniProtKB:P05230

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.