Cited by 147Fibroblast Growth Factor ResearchParathyroid Disorders and TreatmentsConnective Tissue Growth Factor Research

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

Different roles of N‐ and C‐ termini in the functional activity of FGF21

Micanovic, Radmila, Raches, David W., Dunbar, James D., Driver, David A., Bina, Holly A., Dickinson, Craig D., Kharitonenkov, Alexei·2009·Journal of Cellular Physiology

DOI 10.1002/jcp.21675

Open this paper in CoChat — free account

Abstract

Fibroblast growth factor 21 is a member of endocrine FGFs subfamily, along with FGF19 and FGF23. It is emerging as a novel regulator with beneficial effects on a variety of metabolic parameters, including glucose and lipid control. FGF21 activity depends on membrane protein βKlotho that physically complexes with various FGF receptors, thus conferring them the ability to bind FGF21 and activate downstream signaling pathways. FGF21, like other FGFs, folds to a β‐trefoil‐like core region, with disordered N‐ and C‐termini. In order to investigate their role in the activity of FGF21, we have constructed a series of deletion mutants and tested them for their ability to (1) bind βKlotho, analyzed by surface plasmon resonance spectroscopy (2) signal through MAPK phosphorylation and inhibit apoptosis in 3T3‐L1/βKlotho fibroblasts (3) stimulate GLUT1 mRNA upregulation and glucose uptake in 3T3‐L1 adipocytes. Binding studies with βKlotho revealed that the interaction with the co‐receptor involves the C‐terminus, as progressive removal of amino acids from the carboxy end decreased affinity for βKlotho. By contrast, removal of up to 17 amino acids from the N‐terminus had no effect on the interaction with βKlotho. Terminal deletions had greater effect on function, as deletions of six amino acids from the amino‐terminus and only four from the carboxy‐terminus each significantly impacted activity (10‐fold). Of the extreme terminal truncations, with no detectable activity, ΔN17 acted as competitive antagonist while ΔC20 did not. Our structure/function studies show that the C‐terminus is important for βKlotho interaction whereas the N‐terminus likely interacts directly with FGF receptors. J. Cell. Physiol. 219: 227–234, 2009. © 2008 Wiley‐Liss, Inc.

Integrity signals

Registry

Crossref · 10.1002/jcp.21675

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
FGF-21 as a novel metabolic regulator
Kharitonenkov, A., Shiyanova, T. L., Koester, A., Ford, A. M., Micanovic, R., Galbreath, E. J., Sandusky, G. E., Hammond, L. J., Moyers, J. S., Owens, R. A., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23606 · Cited by 2,125
Fibroblast growth factors.
Ornitz, D. M., & Itoh, N. (2001) · Genome biology · doi:10.1186/gb-2001-2-3-reviews3005 · Cited by 1,985
Cellular signaling by fibroblast growth factor receptors
Eswarakumar, V. P., Lax, I., & Schlessinger, J. (2005) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2005.01.001 · Cited by 1,923
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.09.001 · Cited by 1,865
Klotho converts canonical FGF receptor into a specific receptor for FGF23
Urakawa, I., Yamazaki, Y., Shimada, T., Iijima, K., Hasegawa, H., Okawa, K., Fujita, T., Fukumoto, S., & Yamashita, T. (2006) · Nature · doi:10.1038/nature05315 · Cited by 1,865
Endocrine Regulation of the Fasting Response by PPARα-Mediated Induction of Fibroblast Growth Factor 21
Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504
Hepatic Fibroblast Growth Factor 21 Is Regulated by PPARα and Is a Key Mediator of Hepatic Lipid Metabolism in Ketotic States
Badman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495
Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis
Presta, M., Dell’Era, P., Mitola, S. M. F., Moroni, E., Ronca, R., & Rusnati, M. (2005) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2005.01.004 · Cited by 1,283
Receptor Specificity of the Fibroblast Growth Factor Family
Zhang, X., Ibrahimi, O. A., Olsen, S. K., Umemori, H., Mohammadi, M., & Ornitz, D. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601252200 · Cited by 1,164

Show all 39 references

Sorted by citations

Understanding the Physiology of FGF21
Fisher, F. M., & Maratos-Flier, E. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105339 · Cited by 912
The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic
Geng, L., Lam, K. S. L., & Xu, A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0386-0 · Cited by 607
Metabolic messengers: FGF21
Flippo, K. H., & Potthoff, M. J. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00354-2 · Cited by 311
Fibroblast Growth Factor 21—Metabolic Role in Mice and Men
Staiger, H., Keuper, M., Berti, L., Hrabě de Angelis, M., & Häring, H.-U. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00016 · Cited by 270
Hepatokines and metabolism: Deciphering communication from the liver
Jensen-Cody, S. O., & Potthoff, M. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101138 · Cited by 252
Structures of β-klotho reveal a ‘zip code’-like mechanism for endocrine FGF signalling
Lee, S., Choi, J., Mohanty, J., Sousa, L. P., Tome, F., Pardon, E., Steyaert, J., Lemmon, M. A., Lax, I., & Schlessinger, J. (2018) · Nature · doi:10.1038/nature25010 · Cited by 236
Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis
BonDurant, L. D., & Potthoff, M. J. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064800 · Cited by 222
Inventing new medicines: The FGF21 story
Kharitonenkov, A., & Adams, A. C. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2013.12.003 · Cited by 198
Self-citation
Fibroblast Growth Factor 21 Induces Glucose Transporter-1 Expression through Activation of the Serum Response Factor/Ets-Like Protein-1 in Adipocytes
Ge, X., Chen, C., Hui, X. H., Wang, Y., Lam, K. S. L., & Xu, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.248591 · Cited by 181
FGF21 Requires βklotho to Act In Vivo
Adams, A. C., Cheng, C. C., Coskun, T., & Kharitonenkov, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049977 · Cited by 181
Self-citation
Differential Specificity of Endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in Complex with KLB
Yang, C., Jin, C., Li, X., Wang, F., McKeehan, W. L., & Luo, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033870 · Cited by 173
Rational Design of a Fibroblast Growth Factor 21-Based Clinical Candidate, LY2405319
Kharitonenkov, A., Beals, J. M., Micanovic, R., Strifler, B. A., Rathnachalam, R., Wroblewski, V. J., Li, S., Köester, A., Ford, A. M., Coşkun, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058575 · Cited by 168
Self-citation
Rationale-Based Engineering of a Potent Long-Acting FGF21 Analog for the Treatment of Type 2 Diabetes
Hecht, R. I., Li, Y., Sun, J., Belouski, E., Hall, M. P., Hager, T., Yie, J., Wang, W., Winters, D., Smith, S. H., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049345 · Cited by 166
Fibroblast Activation Protein Cleaves and Inactivates Fibroblast Growth Factor 21
Dunshee, D. R., Bainbridge, T. W., Kljavin, N. M., Zavala-Solorio, J., Schroeder, A. C., Chan, R., Corpuz, R., Wong, M., Zhou, W., Deshmukh, G., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.710582 · Cited by 158
FGF21 reloaded: challenges of a rapidly growing field
Kharitonenkov, A., & Larsen, P. J. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.11.003 · Cited by 147
Self-citation
A Novel GLP-1 and FGF21 Dual Agonist Has Therapeutic Potential for Diabetes and Non-Alcoholic Steatohepatitis
Pan, Q., Lin, S., Li, Y., Liu, L., Li, X., Gao, X., Yan, J., Gu, B., Chen, X., Li, W., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.103202 · Cited by 138
Fibroblast Growth Factor Signaling in Metabolic Regulation
Nies, V. J. M., Sancar, G., Liu, W., van Zutphen, T., Struik, D., Yu, R. T., Atkins, A. R., Evans, R. M., Jonker, J. W., & Downes, M. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00193 · Cited by 137
FGFs and metabolism
Kharitonenkov, A. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.07.001 · Cited by 133
Self-citation
Circulating FGF21 proteolytic processing mediated by fibroblast activation protein
Zhen, E. Y., Jin, Z., Ackermann, B. L., Thomas, M. K., & Gutierrez, J. A. (2016) · Biochemical Journal · doi:10.1042/bj20151085 · Cited by 123
Development of a Novel Long-Acting Antidiabetic FGF21 Mimetic by Targeted Conjugation to a Scaffold Antibody
Huang, J., Ishino, T., Chen, G., Rolzin, P., Osothprarop, T. F., Retting, K., Li, L., Jin, P., Matin, M. J., Huyghe, B., et al. (2013) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.204420 · Cited by 121
FGF21 Revolutions: Recent Advances Illuminating FGF21 Biology and Medicinal Properties
Kharitonenkov, A., & DiMarchi, R. D. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.09.007 · Cited by 114
Self-citation
Fundamentals of FGF19 & FGF21 Action In Vitro and In Vivo
Adams, A. C., Coskun, T., Irizarry Rovira, A. R., Schneider, M. A., Raches, D. W., Micanovic, R., Bina, H. A., Dunbar, J. D., & Kharitonenkov, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038438 · Cited by 109
Self-citation
Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex
Kolumam, G., Chen, M. Z., Tong, R., Zavala-Solorio, J., Kates, L., van Bruggen, N., Ross, J., Wyatt, S. K., Gandham, V. D., Carano, R. A. D., et al. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.05.028 · Cited by 108
FGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases
Sonoda, J., Chen, M. Z., & Baruch, A. (2017) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2017-0002 · Cited by 110
Metabolic fibroblast growth factors (FGFs): Mediators of energy homeostasis
Markan, K. R., & Potthoff, M. J. (2016) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2015.09.021 · Cited by 103
Fibroblast growth factor 21 night watch: advances and uncertainties in the field
Kharitonenkov, A., & DiMarchi, R. D. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12580 · Cited by 97
Self-citation
Understanding the Physical Interactions in the FGF21/FGFR/β‐Klotho Complex: Structural Requirements and Implications in FGF21 Signaling
Yie, J., Wang, W., Deng, L., Tam, L., Stevens, J., Chen, M. M., Li, Y., Xu, J., Lindberg, R., Hecht, R., et al. (2012) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2012.01325.x · Cited by 99
Conversion of a Paracrine Fibroblast Growth Factor into an Endocrine Fibroblast Growth Factor
Goetz, R. M., Ohnishi, M., Kır, S., Kurosu, H., Wang, L., Pastor, J. V., Ma, J., Gai, W., Kuro‐o, M., Razzaque, M. S., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.342980 · Cited by 100
FGF19 and FGF21 for the Treatment of NASH—Two Sides of the Same Coin? Differential and Overlapping Effects of FGF19 and FGF21 From Mice to Human
Henriksson, E., & Andersen, B. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.601349 · Cited by 97
Fibroblast growth factor 21 is a metabolic regulator that plays a role in the adaptation to ketosis
Domouzoglou, E. M., & Maratos–Flier, E. (2011) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.001941 · Cited by 93
FGF21: a novel prospect for the treatment of metabolic diseases.
Kharitonenkov, A., & Shanafelt, A. B. (2009) · PubMed · Cited by 91
Self-citation
Fibroblast growth factors, old kids on the new block
Li, X., Wang, C., Xiao, J., McKeehan, W. L., & Wang, F. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.12.014 · Cited by 93
Sustained release of a GLP-1 and FGF21 dual agonist from an injectable depot protects mice from obesity and hyperglycemia
Gilroy, C. A., Capozzi, M. E., Varanko, A. K., Tong, J., D’Alessio, D. A., Campbell, J. E., & Chilkoti, A. (2020) · Science Advances · doi:10.1126/sciadv.aaz9890 · Cited by 85
Klotho Coreceptors Inhibit Signaling by Paracrine Fibroblast Growth Factor 8 Subfamily Ligands
Goetz, R. M., Ohnishi, M., Ding, X., Kurosu, H., Wang, L., Akiyoshi, J., Ma, J., Gai, W., Sidis, Y., Pitteloud, N., et al. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06603-11 · Cited by 86
Plasma FGF21 levels in obese patients undergoing energy-restricted diets or bariatric surgery: a marker of metabolic stress?
Crujeiras, A. B., Gómez-Arbeláez, D., Zulet, M. Á., Carreira, M. C., Sajoux, I., de Luis, D. A., Castro, A. I., Baltar, J., de la Torre, I. B., Sueiro, A. M., et al. (2017) · International Journal of Obesity · doi:10.1038/ijo.2017.138 · Cited by 83
FGF19 and FGF21: In NASH we trust
Talukdar, S., & Kharitonenkov, A. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101152 · Cited by 82
Self-citation
Circulating FGF21 Levels in Human Health and Metabolic Disease
Keuper, M., Häring, H., & Staiger, H. (2019) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-0879-2968 · Cited by 83
Fibroblast activation protein (FAP) as a novel metabolic target
Sanchez-Garrido, M. A., Habegger, K. M., Clemmensen, C., Holleman, C. L., Müller, T. D., Pérez–Tilve, D., Li, P., Agrawal, A., Finan, B., Drucker, D. J., et al. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.07.003 · Cited by 79
Self-citation
Fibroblast growth factor 21, the endocrine FGF pathway and novel treatments for metabolic syndrome
Zhang, J., & Li, Y. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2013.10.021 · Cited by 73
Serum FGF-21 Levels in Type 2 Diabetic Patients
Cheng, X., Zhu, B. L., Jiang, F., & Fan, H. (2011) · Endocrine Research · doi:10.3109/07435800.2011.558550 · Cited by 73
Human FGF-21 Is a Substrate of Fibroblast Activation Protein
Coppage, A. L., Heard, K. R., DiMare, M. T., Liu, Y., Wu, W., Lai, J. H.-S., & Bachovchin, W. W. (2016) · PLoS ONE · doi:10.1371/journal.pone.0151269 · Cited by 71
Fibroblast Growth Factor 21 Analogs for Treating Metabolic Disorders
Zhang, J., & Li, Y. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00168 · Cited by 70
Pharmacokinetics (PK), Pharmacodynamics (PD) and Integrated PK/PD Modeling of a Novel Long Acting FGF21 Clinical Candidate PF-05231023 in Diet-Induced Obese and Leptin-Deficient Obese Mice
Weng, Y., Chabot, J., Bernardo, B. L., Yan, Q., Zhu, Y., Brenner, M. B., Vage, C., Logan, A., Calle, R. A., & Talukdar, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119104 · Cited by 67
The Role of Fibroblast Growth Factor 21 (FGF21) on Energy Balance, Glucose and Lipid Metabolism
Ramos, D. C., Almeda‐Valdés, P., Aguilar-Salinas, C. A., Cuevas-Ramos, G., Cuevas-Sosa, A., & Gomez-Perez, F. J. (2009) · Current Diabetes Reviews · doi:10.2174/157339909789804396 · Cited by 70
The FGF21 Receptor Signaling Complex
Kilkenny, D. M., & Rocheleau, J. V. (2016) · Vitamins and hormones · doi:10.1016/bs.vh.2016.02.008 · Cited by 68
The Saga of Endocrine FGFs
Phan, P., Saikia, B. B., Sonnaila, S., Agrawal, S., Alraawi, Z., Kumar, T. K. S., & Iyer, S. (2021) · Cells · doi:10.3390/cells10092418 · Cited by 70
FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans
Samms, R. J., Lewis, J. E., Norton, L., Stephens, F. B., Gaffney, C. J., Butterfield, T., Smith, D. P., Cheng, C. C., Perfield, J. W., Adams, A. C., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01257 · Cited by 65
Metabolic role of fibroblast growth factor 21 in liver, adipose and nervous system tissues
Lin, X., Liu, Y. B., & Hu, H. (2017) · Biomedical Reports · doi:10.3892/br.2017.890 · Cited by 61
Sulforaphane ameliorates non-alcoholic fatty liver disease in mice by promoting FGF21/FGFR1 signaling pathway
Wu, Y., Ren, Z., Zhu, S., Wu, Y., Wang, G., Zhang, H., Chen, W., He, Z., Ye, X.-L., & Zhai, Q. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00786-2 · Cited by 66
FGF21 Can Be Mimicked In Vitro and In Vivo by a Novel Anti-FGFR1c/β-Klotho Bispecific Protein
Smith, R. J., Duguay, A. N., Bakker, A., Li, P., Weiszmann, J., Thomas, M. R., Alba, B. M., Wu, X., Gupte, J., Li, Y., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061432 · Cited by 59
Fusion of fibroblast growth factor 21 to a thermally responsive biopolymer forms an injectable depot with sustained anti-diabetic action
Gilroy, C. A., Roberts, S., & Chilkoti, A. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.03.015 · Cited by 58
Fibroblast growth factor 21 in chronic kidney disease
Suassuna, P. G. D. A., de Paula, R. B., Sanders‐Pinheiro, H., Moe, O. W., & Hu, M. C. (2018) · Journal of Nephrology · doi:10.1007/s40620-018-0550-y · Cited by 57
Fibroblast Growth Factor 21 Protects against Atherosclerosis via Fine-Tuning the Multiorgan Crosstalk
Jin, L., Lin, Z., & Xu, A. (2016) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2016.40.1.22 · Cited by 52
A Better Anti-Diabetic Recombinant Human Fibroblast Growth Factor 21 (rhFGF21) Modified with Polyethylene Glycol
Huang, Z., Wang, H., Lu, M., Sun, C., Wu, X., Tan, Y., Ye, C., Zhu, G., Wang, X., Cai, L., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020669 · Cited by 51
Fibroblast growth factor 21: an overview from a clinical perspective
Rydén, M. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0003-9 · Cited by 48
Impact of short-term high-fat feeding and insulin-stimulated FGF21 levels in subjects with low birth weight and controls
Vienberg, S. G., Brøns, C., Nilsson, E., Astrup, A., Vaag, A., & Andersen, B. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0039 · Cited by 47
Metabolic actions of fibroblast growth factor 21
Ramos, D. C., Aguilar-Salinas, C. A., & Gomez-Perez, F. J. (2012) · Current Opinion in Pediatrics · doi:10.1097/mop.0b013e3283557d22 · Cited by 46
Molecular elements in FGF19 and FGF21 defining KLB/FGFR activity and specificity
Agrawal, A., Parlee, S. D., Pérez–Tilve, D., Li, P., Pan, J. H., Mroz, P. A., Hansen, A. M. K., Andersen, B., Finan, B., Kharitonenkov, A., et al. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.05.003 · Cited by 42
Self-citation
Structures of ligand-occupied β-Klotho complexes reveal a molecular mechanism underlying endocrine FGF specificity and activity
Kuzina, E. S., Ung, P. M. U., Mohanty, J., Tomé, F., Choi, J., Pardon, E., Steyaert, J., Lax, I., Schlessinger, A., Schlessinger, J., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1822055116 · Cited by 41
Beta-klotho in type 2 diabetes mellitus: From pathophysiology to therapeutic strategies
Hua, S., Liu, Q., Li, J., Fan, M., Yan, K., & Ye, D. (2021) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09661-1 · Cited by 39
Fibroblast Growth Factor 21 Improves Insulin Sensitivity and Synergizes with Insulin in Human Adipose Stem Cell-Derived (hASC) Adipocytes
Lee, D. V., Li, D., Yan, Q., Zhu, Y., Goodwin, B. J., Calle, R. A., Brenner, M. B., & Talukdar, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111767 · Cited by 38
Fibroblast growth factor 21: An emerging pleiotropic regulator of lipid metabolism and the metabolic network
Li, S., Zou, T., Chen, J., Li, J., & You, J. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.06.033 · Cited by 37
Emerging Structure–Function Paradigm of Endocrine FGFs in Metabolic Diseases
Luo, Y., Ye, S., Li, X., & Lu, W. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.12.002 · Cited by 37
Therapeutic Approaches to Alzheimer’s Type of Dementia: A Focus on FGF21 Mediated Neuroprotection
Taliyan, R., Chandran, S. K., & Kakoty, V. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190716101411 · Cited by 35
Metabolic actions of FGF21: molecular mechanisms and therapeutic implications
Ge, X., Wang, Y., Lam, K. S., & Xu, A. (2012) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2012.06.011 · Cited by 35
Prokaryotic soluble expression and purification of bioactive human fibroblast growth factor 21 using maltose-binding protein
Nguyen, A. N., Song, J.-A., Nguyen, M. T., Do, B. H., Kwon, G. G., Park, S. S., Yoo, J., Jang, J., Jin, J., Osborn, M. J., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-16167-x · Cited by 33
Glyco-engineered Long Acting FGF21 Variant with Optimal Pharmaceutical and Pharmacokinetic Properties to Enable Weekly to Twice Monthly Subcutaneous Dosing
Weng, Y., Ishino, T., Sievers, A., Talukdar, S., Chabot, J., Tam, A. S. P., Duan, W., Kerns, K. M., Sousa, E. A., He, T., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-22456-w · Cited by 33
A systematic dissection of sequence elements determining β-Klotho and FGF interaction and signaling
Shi, S. Y., Lu, Y., Richardson, J., Min, X., Weiszmann, J., Richards, W. G., Wang, Z., Zhang, Z., Zhang, J., & Li, Y. (2018) · Scientific Reports · doi:10.1038/s41598-018-29396-5 · Cited by 31
Higher serum levels of fibroblast growth factor 21 in old patients with cachexia
Franz, K., Ost, M., Otten, L., Herpich, C., Coleman, V., Endres, A., Klaus, S., Müller‐Werdan, U., & Norman, K. (2018) · Nutrition · doi:10.1016/j.nut.2018.11.004 · Cited by 31
Circulating FGF19 and FGF21 surge in early infancy from infra- to supra-adult concentrations
Sánchez‐Infantes, D., Gallego-Escuredo, J. M., Díaz, M., Aragonès, G., Sebastiani, G., López‐Bermejo, A., de Zegher, F., Domingo, P., Villarroya, F., & Ibáñez, L. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.2 · Cited by 30
FGF21 as a Therapeutic Reagent
Zhao, Y., Dunbar, J. D., & Kharitonenkov, A. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0887-1_14 · Cited by 30
Self-citation
Stimuli-responsive hydrogel with spatiotemporal co-delivery of FGF21 and H₂S for synergistic diabetic wound repair
Chu, L., Shen, J., Xu, Z., Huang, J., Ning, L., Feng, Z., Jiang, Y., Wu, P., Gao, C., Wang, W., et al. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113749 · Cited by 26
Discovery of a novel fibroblast activation protein (FAP) inhibitor, BR103354, with anti-diabetic and anti-steatotic effects
Cho, J. M., Yang, E. H., Quan, W., Nam, E. H., & Cheon, H. G. (2020) · Scientific Reports · doi:10.1038/s41598-020-77978-z · Cited by 24
N-3 polyunsaturated fatty acids increase hepatic fibroblast growth factor 21 sensitivity via a PPAR-γ-β-klotho pathway
Yang, W., Chen, X., Liu, Y., Chen, M., Jiang, X., Shen, T., Li, Q., Yang, Y., & Ling, W. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201601075 · Cited by 25
Design and Evaluation of Lyophilized Fibroblast Growth Factor 21 and Its Protection against Ischemia Cerebral Injury
Yang, X., Hui, Q., Yu, B., Huang, Z., Zhou, P., Wang, P., Wang, Z., Pang, S., Li, J., Wang, H., et al. (2017) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.7b00588 · Cited by 22
Identification of a second Klotho interaction site in the C terminus of FGF23
Agrawal, A., Ni, P., Agoro, R., White, K. E., & DiMarchi, R. D. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108665 · Cited by 22
Efruxifermin, a long‐acting Fc‐fusion FGF21 analogue, reduces body weight gain but does not increase sympathetic tone or urine volume in Sprague Dawley rats
Tillman, E. J., Brock, W. J., & Rolph, T. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15725 · Cited by 22
Large-scale expression, purification, and glucose uptake activity of recombinant human FGF21 in Escherichia coli
Zhang, M., Jiang, X., Su, Z., Lin, J., Xiang, Q., Yang, Z., Huang, Y., & Li, X. (2011) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-011-3427-8 · Cited by 21
Understanding the Structure-Function Relationship between FGF19 and Its Mitogenic and Metabolic Activities
Wu, X., & Li, Y. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0887-1_13 · Cited by 21
A Novel Approach to Improve the Function of FGF21
Smith, R. W., Duguay, A. N., Weiszmann, J., Stanislaus, S., Belouski, E., Cai, L., Yie, J., Xu, J., Gupte, J., Wu, X., et al. (2013) · BioDrugs · doi:10.1007/s40259-013-0013-x · Cited by 20
Mechanistic Investigation of the Preclinical Pharmacokinetics and Interspecies Scaling of PF-05231023, a Fibroblast Growth Factor 21–Antibody Protein Conjugate
Giragossian, C., Vage, C., Li, J., Pelletier, K. B., Piche‐Nicholas, N., Rajadhyaksha, M., Liras, J. L., Logan, A., Calle, R. A., & Weng, Y. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.061713 · Cited by 20
Fibroblast growth factor-21 (FGF21) administration to early-lactating dairy cows. II. Pharmacokinetics, whole-animal performance, and lipid metabolism
Caixeta, L. S., Giesy, S. L., Krumm, C. S., Perfield, J. W., Butterfield, A. M., & Boisclair, Y. R. (2019) · Journal of Dairy Science · doi:10.3168/jds.2019-16696 · Cited by 20
Emerging roles of fibroblast growth factor 21 in critical disease
Fang, Y., Li, Y., Yang, F., Wu, G., & Jiang, X. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1053997 · Cited by 20
Eccentric exercise increases circulating fibroblast activation protein α but not bioactive fibroblast growth factor 21 in healthy humans
Parmar, B., Lewis, J. E., Samms, R. J., Ebling, F. J. P., Cheng, C., Adams, A. C., Mallinson, J. E., Cooper, S., Taylor, T., Ghasemi, R., et al. (2018) · Experimental Physiology · doi:10.1113/ep086669 · Cited by 19
Evolution of Protein Physical Structures in Insect Chemosensory Systems
Picimbon, J. (2019) · Springer eBooks · doi:10.1007/978-3-030-05165-5_10 · Cited by 17
BV2 Membrane‐Coated PEGylated‐Liposomes Delivered hFGF21 to Cortical and Hippocampal Microglia for Alzheimer's Disease Therapy
Wang, H., Yang, W. H., Xu, L., Han, Y., Lin, Y., Lu, C., Kim, K., Zhao, Y., & Yu, X. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202400125 · Cited by 17
Fibroblast growth factor 21 in dairy cows: current knowledge and potential relevance
Eder, K., Geßner, D. K., & Ringseis, R. (2021) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-021-00621-y · Cited by 18
A Unique FGF23 with the Ability to Activate FGFR Signaling through Both αKlotho and βKlotho
Wu, X., Weiszmann, J., Ge, H., Baribault, H., Stevens, J. L., Hawkins, N., Vonderfecht, S. L., Gardner, J., Gupte, J., Sheng, J., et al. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.02.027 · Cited by 17
Novel Sandwich Immunoassays for The Measurement of Total and Active Fgf21
Umberger, T. S., Sloan, J. H., Chen, J., Cheng, C., Siegel, R. W., Qian, Y., Troutt, J. S., & Konrad, R. J. (2014) · Bioanalysis · doi:10.4155/bio.14.241 · Cited by 16
Discovery of an artificial peptide agonist to the fibroblast growth factor receptor 1c/βKlotho complex from random peptide T7 phage display
Sakamoto, K., Kawata, Y., Masuda, Y., Umemoto, T., Ito, T., Asami, T., Takekawa, S., Ohtaki, T., & Inooka, H. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.10.009 · Cited by 15
Exploring endocrine FGFs - structures, functions and biomedical applications
Phan, P. (2024) · International Journal of Biochemistry and Molecular Biology · doi:10.62347/palk2137 · Cited by 16
FAP finds FGF21 easy to digest
Gillum, M. P., & Potthoff, M. J. (2016) · Biochemical Journal · doi:10.1042/bcj20160004 · Cited by 14
β-Klotho as novel therapeutic target in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A narrative review
Meroni, M., Dongiovanni, P., Tiano, F., Piciotti, R., Alisi, A., & Panera, N. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117608 · Cited by 13
Efficacy of a combination of high and low dosage of PEGylated FGF-21 in treatment of diabetes in db/db mice
Xu, P., Zhang, Y., Song, L., Khoso, M. H., Li, J., Jiang, X., He, J., Li, J., Ma, X., Ren, G., et al. (2016) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.09.019 · Cited by 12
FGF21: A Sharp Weapon in the Process of Exercise to Improve NAFLD
Wang, Z., Sun, T., Yu, J., Li, S., Gong, L., & Zhang, Y. (2023) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2812351 · Cited by 12
Balanced Coagonist of GLP-1 and Glucagon Receptors Corrects Dyslipidemia by Improving FGF21 Sensitivity in Hamster Model
PATEL, V. G., Joharapurkar, A. A., Kshirsagar, S. G., Patel, H., Pandey, D., Patel, D. N., Sutariya, B., Patel, M. S., Bahekar, R. H., & Jain, M. R. (2017) · Drug Research · doi:10.1055/s-0043-118808 · Cited by 11
Development of Zalfermin, a Long-Acting Proteolytically Stabilized FGF21 Analog
Sass‐Ørum, K., Tagmose, T. M., Olsen, J., Sjölander, A., Wahlund, P., Han, D., Vegge, A., Reedtz‐Runge, S., Wang, Z., Gao, X., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00391 · Cited by 11
Identification of BR102910 as a selective fibroblast activation protein (FAP) inhibitor
Jung, H. J., Nam, E. H., Park, J. Y., Ghosh, P., & Kim, I. S. (2021) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2021.127846 · Cited by 10
Circulating fibroblast growth factor 21 is reduced, whereas its production is increased in a fat depot-specific manner in cold-acclimated rats
Sepa-Kishi, D. M., & Ceddia, R. B. (2018) · Adipocyte · doi:10.1080/21623945.2018.1504591 · Cited by 10
FGF Pyramus Has a Transmembrane Domain and Cell-Autonomous Function in Polarity
Stepanik, V. A., Sun, J., & Stathopoulos, A. (2020) · Current Biology · doi:10.1016/j.cub.2020.06.006 · Cited by 10

Authors: Micanovic, R., Raches, D. W., Dunbar, J. D., Driver, D. A., Bina, H. A., Dickinson, C. D., & Kharitonenkov, A.
Affiliations: Eli Lilly (United States) (US)
Corresponding author: Micanovic, Radmila
ORCID: Micanovic, Radmila
Kharitonenkov, Alexei
Venue: Journal of Cellular Physiology
Publisher: Wiley
Published: 2008-12-30
Volume: 219
Issue: 2
Pages: 227-234
ISSN: 0021-9541 (ISSN-L)
1097-4652
DOI: 10.1002/jcp.21675
OpenAlex: W2074337024
Cited by: 146
References: 39
Citations by year: 2026: 5 · 2025: 5 · 2024: 10 · 2023: 13 · 2022: 3 · 2021: 10 · 2020: 10 · 2019: 7 · 2018: 14 · 2017: 11 · 2016: 12 · 2015: 9 · 2014: 3 · 2013: 5 · 2012: 16
FWCI: 1.78
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Cellular Physiology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
Keywords: FGF21, β-Klotho, N-terminus, C-terminus, structure functions, fibroblast growth factor receptor, protein-protein interaction, β-trefoil fold, MAPK signaling, GLUT1, glucose uptake, adipocytes, 3T3-L1 fibroblasts, competitive antagonists
MeSH terms: Fibroblast Growth Factor-23, Klotho Proteins, Animals, Fibroblast Growth Factors, Fibroblasts, Membrane Proteins, Mutation, 3T3 Cells, Apoptosis, Protein Structure, Secondary, Protein Structure, Tertiary, Receptors, Fibroblast Growth Factor, Adipocytes, Surface Plasmon Resonance, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Glucose Transporter Type 1, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Different roles of N‐ and C‐ termini in the functional activity of FGF21

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks