The GDNF/RET signaling pathway and human diseases
Glial cell line-derived neurotrophic factor (GDNF) and related molecules, neurturin, artemin and persephin, signal through a unique multicomponent receptor system consisting of RET tyrosine kinase and glycosyl-phosphatidylinositol-anchored coreceptor (GFRalpha1-4). These neurotrophic factors promote the survival of various neurons including peripheral autonomic and sensory neurons as well as central motor and dopamine neurons, and have been expected as therapeutic agents for neurodegenerative diseases. In addition, it turned out that the GDNF/RET signaling plays a crucial role in renal development and regulation of spermatogonia differentiation. RET mutations cause several human diseases such as papillary thyroid carcinoma, multiple endocrine neoplasia types 2A and 2B, and Hirschsprung's disease. The mutations resulted in RET activation or inactivation by various mechanisms and the biological properties of mutant proteins appeared to be correlated with disease phenotypes. The signaling pathways activated by GDNF or mutant RET are being extensively investigated to understand the molecular mechanisms of disease development and the physiological roles of the GDNF family ligands.
Low frequency of rearrangements of the ret and trk proto-oncogenes in Japanese thyroid papillary carcinomas
PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas
Presence of aberrant transcripts of ret proto-oncogene in a human papillary thyroid carcinoma cell line
Developmentally regulated expression of a human "finger"-containing gene encoded by the 5' half of the ret transforming gene.
Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B
A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma
Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease
Low rate of ret proto-oncogene activation (PTC/retTPC) in papillary thyroid carcinomas from Saudi Arabia
The full oncogenic activity of Ret/ptc2 depends on tyrosine 539, a docking site for phospholipase Cgamma.
A mutation at tyrosine 1062 in MEN2A-Ret and MEN2B-Ret impairs their transforming activity and association with shc adaptor proteins.
A mutation in the RET proto-oncogene in Hirschsprung's disease affects the tyrosine kinase activity associated with multiple endocrine neoplasia type 2A and 2B
GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF
Glial cell line-derived neurotrophic factor signals through the RET receptor and activates mitogen-activated protein kinase.
RET alternate splicing influences the interaction of activated RET with the SH2 and PTB domains of Shc, and the SH2 domain of Grb2
Development of medullary thyroid carcinoma in transgenic mice expressing the RET protooncogene altered by a multiple endocrine neoplasia type 2A mutation
A duplication of 12 bp in the critical cysteine rich domain of the RET proto-oncogene results in a distinct phenotype of multiple endocrine neoplasia type 2A
Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins
Neurturin shares receptors and signal transduction pathways with glial cell line-derived neurotrophic factor in sympathetic neurons
DNA methylation of colon mucosa in ulcerative colitis patients: correlation with inflammatory status
Novel mutations at RET ligand genes preventing receptor activation are associated to Hirschsprung's disease
Site-specific gene expression and localization of growth factor ligand receptors RET, GFRα1 and GFRα2 in human adult colon
Targeting RET to induce medullary thyroid cancer cell apoptosis: an antagonistic interplay between PI3K/Akt and p38MAPK/caspase-8 pathways
VEGF-A165 potently induces human blood-nerve barrier endothelial cell proliferation, angiogenesis, and wound healing in vitro
Effects of P2Y1 receptor on glial fibrillary acidic protein and glial cell line-derived neurotrophic factor production of astrocytes under ischemic condition and the related signaling pathways
Identification of human SEP1 as a glial cell line-derived neurotrophic factor-inducible protein and its expression in the nervous system
Identification of RET gene fusion by exon array analyses in "pan-negative" lung cancer from never smokers
HSV-mediated transfer of artemin overcomes myelin inhibition to improve outcome after spinal cord injury
Mechanisms of Disease: cancer targeting and the impact of oncogenic RET for medullary thyroid carcinoma therapy
Glial cell-derived neurotrophic factor upregulates the expression and activation of matrix metalloproteinase-9 in human pancreatic cancer
Antitumor capacity of a dominant-negative RET proto-oncogene mutant in a medullary thyroid carcinoma model
RET proto-oncogene: a review and update of genotype-phenotype correlations in hereditary medullary thyroid cancer and associated endocrine tumors
Cellular effects and antitumor activity of RET inhibitor RPI-1 on MEN2A-associated medullary thyroid carcinoma
GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region
A complex additive model of inheritance for Hirschsprung disease is supported by both RET mutations and predisposing RET haplotypes
Screening for PTB domain binding partners and ligand specificity using proteome-derived NPXY peptide arrays
A targeting mutation of tyrosine 1062 in Ret causes a marked decrease of enteric neurons and renal hypoplasia
Phosphotyrosine 1062 is critical for the in vivo activity of the Ret9 receptor tyrosine kinase isoform
Expression of glial cell-derived neurotrophic factor and its receptor in the stem-cell-containing human limbal epithelium
Neurotrophin and GDNF family ligand receptor expression in vagal sensory nerve subtypes innervating the adult guinea pig respiratory tract
Autoimmune Polyendocrine Syndromes
This feed focuses on a rare genetic condition called Autoimmune Polyendocrine Syndromes, which are characterized by autoantibodies against multiple endocrine organs. This can lead to Type I Diabetes.
Cell Signaling by Tyrosine Kinases
Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.