A network map of GDNF/RET signaling pathway in physiological and pathological conditions

• Published in: Journal of cell communication and signaling 2023-09, Vol.17 (3), p.1089-1095
• Main Authors: Mol, Praseeda, Balaya, Rex Devasahayam Arokia, Dagamajalu, Shobha, Babu, Sreeranjini, Chandrasekaran, Pavithra, Raghavan, Reshma, Suresh, Sneha, Ravishankara, Namitha, Raju, Anu Hemalatha, Nair, Bipin, Modi, Prashant Kumar, Mahadevan, Anita, Prasad, Thottethodi Subrahmanya Keshava, Raju, Rajesh
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Catalysis; Cell Biology; Gene regulation; Glial cell line-derived neurotrophic factor; Glial cells; Glycosylphosphatidylinositol; Kinases; Life Sciences; Morphogenesis; Multi‐component receptor system; Nervous system; Neuronal-glial interactions; Neurotrophic factors; Nuts and Bolts; Phosphatidylinositol; Post‐translational modifications; Protein-tyrosine kinase receptors; Protein–protein interactions; Receptor tyrosine kinases; Ret protein; Signal transduction; Signaling network; Spermatogenesis; Transfection
• ISSN: 1873-9601; 1873-961X
• DOI: 10.1007/s12079-023-00726-1

Glial cell line-derived neurotrophic factor (GDNF) signals through a multi-component receptor system predominantly consisting of glycosyl-phosphatidylinositol-anchored GDNF family receptor alpha-1 (GFRα1) and the Rearranged during transfection (RET) receptor tyrosine kinase. GDNF/RET signaling is vital to the central and peripheral nervous system, kidney morphogenesis, and spermatogenesis. In addition, the dysregulation of the GDNF/RET signaling has been implicated in the pathogenesis of cancers. Despite the extensive research on GDNF/RET signaling, a molecular network of reactions induced by GDNF reported across the published literature. However, a comprehensive GDNF/RET pathway resource is currently unavailable. We describe an integrated signaling pathway reaction map of GDNF/RET consisting of 1151 molecular reactions. These include information pertaining to 52 molecular association events, 70 enzyme catalysis events, 36 activation/inhibition events, 22 translocation events, 856 gene regulation events, and 115 protein-level expression events induced by GDNF in diverse cell types. We developed a comprehensive GDNF/RET signaling network map based on these molecular reactions. The pathway map was made accessible through WikiPathways database ( https://www.wikipathways.org/index.php/Pathway:WP5143 ). Graphical abstract Biocuration and development of gene regulatory network map of GDNF/RET signaling pathway