The Signaling Pathway of Growth Differentiation Factor 15 and Its Receptor GFRAL / 中国生物化学与分子生物学报

ABSTRACT

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor β (TGF-β) superfamily, is a new class of dimeric polypeptides with very low homology with other TGF-β family members. GDF15 was originally found in activated macrophages where it was secreted into the body circulation in two different cellular pathways. Moreover, GDF15 as a stress protein is widely involved in many signal pathways such as phosphoinositide 3-kinase / protein kinase B, extracellular signal-regulated kinase, c-Jun N-terminal kinase and nuclear factor-κB, and so on, and thus involved in the regulation of various disease processes. In addition, GDF15 as a new type of stress molecule acts as a biomarker and plays a regulatory role in obesity, weight loss, cancer development, cardiovascular disease, inflammation and autoimmune diseases. Glial-derived neurotrophic factor receptor alpha-like (GFRAL) is the specific receptor of GDF15, and the molecular basis of its activity is to conduct signal transduction through GFRAL-dependent binding into multimers. The intervention of the GDF15-GFRAL signaling pathway has a great application potential in the development of weight-loss drugs and cancer prognosis recovery drugs. This review focuses on the recent progress of GDF15-GFRAL and its related signaling pathways, the molecular structure of GDF15 and GFRAL, and the mechanism of GDF15-GFRAL signaling pathway, which reveals the role and regulatory ability of GDF15 as a biomarker in the development of disease and provides new insights in potential and treatment strategies of regulating the GDF15-GFRAL signaling pathway in related diseases.