growth differentiation factor 15   Click here for help

GtoPdb Ligand ID: 9735

Abbreviated name: GDF15
Synonyms: macrophage inhibitory cytokine-1 | MIC-1 | MIC1 | PTGFB
Comment: GDF15 is a TGFβ family protein. A commentary on the function(s) of GDF15 was published in 2017 [6]. Experimental evidence indicates that the biological effects of GDF15 are mediated by signalling via a GFRAL/Ret complex [2,5-6,8].
GDF15 promotes nausea and vomiting (emesis), and elevated levels have been associated with pregnancy-induced morning sickness and the risk of hyperemesis gravidarum [3]. Disrupting the formation or function of the GDF15/GFRAL/Ret complex is a mechanism being explored for the mitigation of chemotherapy-induced nausea, cachexia and malaise [1,4,7].
Species: Human
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References
1. Borner T, Tinsley IC, Milliken BT, Doebley SA, Najjar NR, Kerwood DJ, De Jonghe BC, Hayes MR, Doyle RP. (2023)
Creation of a Peptide Antagonist of the GFRAL-RET Receptor Complex for the Treatment of GDF15-Induced Malaise.
J Med Chem, 66 (16): 11237-11249. [PMID:37506293]
2. Emmerson PJ, Wang F, Du Y, Liu Q, Pickard RT, Gonciarz MD, Coskun T, Hamang MJ, Sindelar DK, Ballman KK et al.. (2017)
The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL.
Nat Med, 23 (10): 1215-1219. [PMID:28846098]
3. Fejzo M, Rocha N, Cimino I, Lockhart SM, Petry C, Kay RG, Burling K, Barker P, George AL, Yasara N et al.. (2023)
Fetally-encoded GDF15 and maternal GDF15 sensitivity are major determinants of nausea and vomiting in human pregnancy.
biorxiv, Preprint. DOI: 10.1101/2023.06.02.542661
4. Lee BY, Jeong J, Jung I, Cho H, Jung D, Shin J, Park JK, Park E, Noh S, Shin S et al.. (2023)
GDNF family receptor alpha-like antagonist antibody alleviates chemotherapy-induced cachexia in melanoma-bearing mice.
J Cachexia Sarcopenia Muscle, 14 (3): 1441-1453. [PMID:37017344]
5. Mullican SE, Lin-Schmidt X, Chin CN, Chavez JA, Furman JL, Armstrong AA, Beck SC, South VJ, Dinh TQ, Cash-Mason TD et al.. (2017)
GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates.
Nat Med, 23 (10): 1150-1157. [PMID:28846097]
6. O'Rahilly S. (2017)
GDF15-From Biomarker to Allostatic Hormone.
Cell Metab, 26 (6): 807-808. [PMID:29195860]
7. Suriben R, Chen M, Higbee J, Oeffinger J, Ventura R, Li B, Mondal K, Gao Z, Ayupova D, Taskar P et al.. (2020)
Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice.
Nat Med, 26 (8): 1264-1270. [PMID:32661391]
8. Yang L, Chang CC, Sun Z, Madsen D, Zhu H, Padkjær SB, Wu X, Huang T, Hultman K, Paulsen SJ et al.. (2017)
GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand.
Nat Med, 23 (10): 1158-1166. [PMID:28846099]