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These data provide the first evidence for a physiologic role of these isoforms in RET pathway function.
Significantly, we show that introduction of mapk10 (zeige MAPK10 Proteine) mutations into ret heterozygotes enhanced the ENS deficit, supporting MAPK10 (zeige MAPK10 Proteine) as a Hirschsprung disease (HSCR (zeige EDNRB Proteine)) susceptibility locus. Our studies demonstrate that ret heterozygous zebrafish is a sensitized model, with many significant advantages over existing murine models, to explore the pathophysiology and complex genetics of HSCR (zeige EDNRB Proteine).
RET expression is investigated within the brain of zebrafish; both RET protein and mRNA are observed.
In animals lacking Ret or Gfra3 (zeige GFRA3 Proteine) function, myogenic gene expression is reduced in forming opercular muscles, but not in non-opercular muscles derived from the same muscle anlagen.
evaluation of noncoding sequences at the zebrafish ret locus conserved among teleosts, and at the human RET locus, conserved among mammals
genes beyond RET may be implicated in the genesis of sporadic cases of HD
study provided useful information on RET variants that should be subjected to further study
Review of RET mutations and mechanisms in medullary thyroid cancer.
The cardiac GFRA2 (zeige GFRA2 Proteine) signaling pathway is distinct from the canonical pathway dependent on the RET tyrosine kinase (zeige TXK Proteine).
identified four genomic rearrangements involving the genes BRAF, RET, and ROS1
Detection of Gene Rearrangements in Circulating Tumor Cells: Examples of ALK-, ROS1 (zeige ROS1 Proteine)-, RET-Rearrangements in Non-Small-Cell Lung Cancer and ERG (zeige ERG Proteine)-Rearrangements in Prostate Cancer.(
These findings support the role of RET in the development of the enteric nervous system but underline the importance of other genetic or environmental factors contributing to the gastrointestinal phenotype of the disease. Somehow, this RET R114H mutation proved to have a role in the etiology of both CIPO and HSCR (zeige EDNRB Proteine) and could contribute to a more diffuse imbalance of gut (zeige GUSB Proteine) dysmotility.
High RET expression is associated with perineurial invasion of pancreatic adenocarcinoma.
RET expression was significantly greater in patients with Extraskeletal myxoid chondrosarcoma relative to other types of sarcomas except for liposarcoma
RET gene rearrangement plays a role in the pathogenesis of papillary thyroid cancer.
Patients with high- and moderate-risk RET mutations had similar OS and development of distant metastatic disease after medullary thyroid carcinoma diagnosis and therefore similarly aggressive clinical courses. High-risk connotes increased disease aggressiveness; thus, future guidelines should consider RET mutation classification by disease onset (early vs late) rather than by risk (high vs moderate).
The cardiac GFRA2 (zeige GFRA2 Proteine) signaling pathway is distinct from the canonical pathway dependent on the RET tyrosine kinase (zeige TYRO3 Proteine).
Ret is essential to mediate GDNF's neuroprotective and neuroregenerative effect in a Parkinson disease mouse model.
Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases.
Authors did not find evidence for genetic interaction between Ret and Sema3d (zeige SEMA3D Proteine) affecting survival, presence of myenteric plexus or intestine transcriptome.
findings uncover a novel spinal circuit that mediates crosstalk between touch and pain pathways and suggest that some early RET positive Dorsal Horn neurons could function as pain "gating" neurons.
Using an organ culture system for prostate development and Ret mutant mice, we demonstrate that RET-mediated GDNF signaling in UGS increases proliferation of mesenchyme cells and suppresses androgen-induced proliferation and differentiation of prostate epithelial cells, inhibiting prostate development.
we described a RET-ER81 (zeige ETV1 Proteine)-Neuregulin1 signaling pathway in neurons innervating Pacinian corpuscle somatosensory end organs, which is essential for communication between the innervating axon and the end organ
Hox (zeige MSH2 Proteine) proteins coordinate motor neuron differentiation and connectivity programs through Ret/Gfra genes.
Ret and Gfra2 (zeige GFRA2 Proteine) null mice display comparable early central projection deficits, but Gfra2 (zeige GFRA2 Proteine) null rapidly adapting mechanoreceptors recover later.
This gene, a member of the cadherin superfamily, encodes one of the receptor tyrosine kinases, which are cell-surface molecules that transduce signals for cell growth and differentiation. This gene plays a crucial role in neural crest development, and it can undergo oncogenic activation in vivo and in vitro by cytogenetic rearrangement. Mutations in this gene are associated with the disorders multiple endocrine neoplasia, type IIA, multiple endocrine neoplasia, type IIB, Hirschsprung disease, and medullary thyroid carcinoma. Two transcript variants encoding different isoforms have been found for this gene. Additional transcript variants have been described but their biological validity has not been confirmed.
proto-oncogene tyrosine-protein kinase receptor Ret
, receptor tyrosine kinase
, ret proto-oncogene
, proto-oncogene tyrosine-protein kinase receptor Ret-like
, RET transforming sequence
, cadherin family member 12
, cadherin-related family member 16
, hydroxyaryl-protein kinase
, proto-oncogene c-Ret
, ret proto-oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease)
, Ret gene for receptor tyrosin
, Ret proto-oncogene (multiple endocrine neoplasia MEN2A MEN2B and medullary thyroid carcinoma 1 Hirschsprung disease)
, ret tyrosine kinase