betaKLOTHO IS REQUIRED FOR FGF21 SIGNALING THROUGH FGFR1c AND FGFR3c.

@article{citeulike:2296871, 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. Co-expression of betaKlotho and FGFR1c on BaF3 cells enabled FGF21, but not FGF23, to activate receptor signaling. Conversely, co-expression 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, upregulation of glucose transporter 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.}, address = {Signaling Molecules Research Laboratory (M.S., Y.U., K.M.-M., J.O., M.K., M.A., A.K.-K., S.O., T.I.), and Institute for Biological Resources and Functions (Y.K.), National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.}, author = {Suzuki, Masashi and Uehara, Yuriko and Motomura-Matsuzaka, Kaori and Oki, Junko and Koyama, Yoshinori and Kimura, Miho and Asada, Masahiro and Komi-Kuramochi, Akiko and Oka, Syuichi and Imamura, Toru }, citeulike-article-id = {2296871}, doi = {10.1210/me.2007-0313}, issn = {0888-8809}, journal = {Mol Endocrinol}, month = {January}, posted-at = {2008-01-28 09:06:34}, priority = {2}, title = {{beta}KLOTHO IS REQUIRED FOR FGF21 SIGNALING THROUGH FGFR1c AND FGFR3c.}, url = {http://dx.doi.org/10.1210/me.2007-0313}, year = {2008} }

TY - JOUR ID - citeulike:2296871 L3 - citeulike-article-id:2296871 TI - {beta}KLOTHO IS REQUIRED FOR FGF21 SIGNALING THROUGH FGFR1c AND FGFR3c. JF - Mol Endocrinol AD - Signaling Molecules Research Laboratory (M.S., Y.U., K.M.-M., J.O., M.K., M.A., A.K.-K., S.O., T.I.), and Institute for Biological Resources and Functions (Y.K.), National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. SN - 0888-8809 N2 - 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. Co-expression of betaKlotho and FGFR1c on BaF3 cells enabled FGF21, but not FGF23, to activate receptor signaling. Conversely, co-expression 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, upregulation of glucose transporter 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. AU - Suzuki, Masashi AU - Uehara, Yuriko AU - Motomura-Matsuzaka, Kaori AU - Oki, Junko AU - Koyama, Yoshinori AU - Kimura, Miho AU - Asada, Masahiro AU - Komi-Kuramochi, Akiko AU - Oka, Syuichi AU - Imamura, Toru PY - 2008/01/10/ UR - http://dx.doi.org/10.1210/me.2007-0313 ER -