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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
RET p.C634F mutation is associated with Multiple Endocrine Neoplasia Type 2A with Cutaneous Lichen Amyloidosis.
These data support the inclusion of patients bearing RET alterations in ongoing and future molecularly enriched clinical trials to explore RXDX-105 efficacy across a variety of tumor types.
These results implicate EGFR (zeige EGFR Proteine) as a key regulator of RET activation in A+AD and suggest that EGFR (zeige EGFR Proteine) inhibitors may be therapeutic in patients with A+AD tumors even in the absence of an EGFR (zeige EGFR Proteine) or RET mutation.
In a cohort of MEN 2 families, the distribution of RET mutations in Denmark appears to differ from that of other populations. Mutations in codon 611 were the most prevalent, followed by more frequently reported mutations. This might be due to a possible founder effect for the p.C611Y mutation.
RET inhibitors could both impair primary tumor growth and tumor dissemination, thereby providing a potential therapeutic advantage when used in combination with aromatase (zeige CYP19A1 Proteine) inhibitors in postmenopausal ER+ breast cancers.
exposure of medullary thyroid cancer cells to a tri (zeige VANGL2 Proteine)-substituted naphthalene diimide resulted in a significant antiproliferative activity paralleled by inhibition of RET expression
Our data show that RET expression promotes a more mesenchymal phenotype with reduced cell-cell adhesion and increased invasiveness in papillary thyroid carcinoma cell models, but is more important for tumour cell survival, proliferation and anoikis resistance in medullary thyroid carcinoma models. Our data suggest that the RET51 isoform plays a more prominent role in mediating these processes compared to RET9.
From this case series, the largest such experience to date, it is concluded that the RET(K666N) variant is likely pathogenic and associated with low penetrance of medullary thyroid carcinoma.
Multilayer OMIC data analysis uncovered methylation hallmarks in genetically defined Medullary thyroid carcinoma (MTC (zeige MT1A Proteine)) and revealed JAK (zeige JAK3 Proteine)/Stat (zeige STAT1 Proteine) signaling effector STAT3 (zeige STAT3 Proteine) as a potential therapeutic target for the treatment of RET(M918T) MTCs
DNA mutational analysis of RET germline mutations associated with medullary thyroid carcinoma in a Druze family.
Compromised Survival of Cerebellar Molecular Layer Interneurons Lacking GDNF Receptors GFRalpha1 (zeige GFRA1 Proteine) or RET Impairs Normal Cerebellar Motor Learning
Data show that NEDL2 regulates GDNF/Ret/Akt pathway depends on its Nedd8 ligase activity rather than ubiquitin ligase activity.
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
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