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RET

GeneName

RET

Summary

RET, also known as reverse transcriptase or PTC, is a 124kDa transmembrane receptor protein tyrosine kinase that is expressed in various tissues, including the nervous system and kidney. It is localised to the plasma membrane and endosomal membranes, and plays a critical role in several biological processes such as axon guidance, enteric nervous system development, and neuronal maturation. RET functions primarily through its receptor activity, mediating signalling pathways including the glial cell-derived neurotrophic factor (GDNF) signalling pathway and the MAPK cascade. Its ability to bind ATP and calcium ions further supports its role in signal transduction and cellular responses to external stimuli.

Importance

RET is relevant to: - Developmental biology, particularly in the context of neural crest cell migration and organogenesis, including the formation of the enteric nervous system and kidneys. - Cancer research, as mutations in RET are implicated in various cancers, including multiple endocrine neoplasia type 2 (MEN2). - Neurobiology, due to its involvement in neuron maturation and axonogenesis, which are essential for proper nervous system function. - Regenerative medicine, as understanding RET signalling pathways may inform strategies for tissue repair and regeneration.

Top Products

For researchers investigating RET, we highly recommend the top-selling recombinant antibody, Anti-Ret antibody [EPR2871] (ab134100). This antibody has been validated for a variety of applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), immunoprecipitation (IP), and ELISA, making it a versatile tool for your research needs. With 64 citations, it is well-regarded in the scientific community, reflecting its reliability and effectiveness in detecting RET. This product is an excellent choice for those seeking consistent performance in their experiments.

Abcam Product Citation Summary

The data indicates that the RET target is being investigated in the context of lung cancer, specifically focusing on RET fusion genes and resistance to the drug vandetanib. The use of Abcam antibodies in both immunohistochemistry and western blotting highlights the importance of RET in cancer research.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab134100
Human
IHC
Lung adenocarcinoma
27150058
ab134100
Human
WB
Lung cancer cells
29434222

Function

Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) (PubMed:20064382, PubMed:20616503, PubMed:20702524, PubMed:21357690, PubMed:21454698, PubMed:24560924, PubMed:28846097, PubMed:28846099, PubMed:28953886, PubMed:31118272). In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation (PubMed:21994944, PubMed:23333276, PubMed:28846097, PubMed:28846099, PubMed:28953886). GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways (PubMed:21994944, PubMed:23333276, PubMed:24560924, PubMed:25242331, PubMed:28846097, PubMed:28846099, PubMed:28953886). Acts as a dependence receptor via the GDNF-GFRA1 signaling: in the presence of the ligand GDNF in somatotrophs within pituitary, promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF (PubMed:20616503, PubMed:21994944). Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses (PubMed:28846097, PubMed:28846099, PubMed:28953886). Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner (PubMed:20702524, PubMed:21357690). Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage (PubMed:21357690). Triggers the differentiation of rapidly adapting (RA) mechanoreceptors (PubMed:20064382). Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 (PubMed:21454698).

Isoform 1

Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL.

Involvement in disease

Hirschsprung disease 1

HSCR1

A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child.

None

The disease is caused by variants affecting the gene represented in this entry.

Medullary thyroid carcinoma

MTC

Rare tumor derived from the C cells of the thyroid. Three hereditary forms are known, that are transmitted in an autosomal dominant fashion: (a) multiple neoplasia type 2A (MEN2A), (b) multiple neoplasia type IIB (MEN2B) and (c) familial MTC (FMTC), which occurs in 25-30% of MTC cases and where MTC is the only clinical manifestation.

None

The disease is caused by variants affecting the gene represented in this entry.

Multiple neoplasia 2B

MEN2B

Uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophthalmic abnormalities, and ganglioneuromas of the intestine tract. Then the disease progresses rapidly with the development of metastatic MTC and a pheochromocytome in 50% of cases.

None

The disease is caused by variants affecting the gene represented in this entry.

Pheochromocytoma

PCC

A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Multiple neoplasia 2A

MEN2A

The most frequent form of medullary thyroid cancer (MTC). It is an inherited cancer syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism.

None

The disease is caused by variants affecting the gene represented in this entry.

Various chromosomal aberrations involving RET are known. Some of them have been found in papillary thyroid carcinomas (PTCs) (PubMed:10439047, PubMed:10980597, PubMed:12787916, PubMed:2406025). Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene (PubMed:2406025). Inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene. Translocation t(10;14)(q11;q32) with GOLGA5 generates the RET/GOLGA5 (PTC5) oncogene (PubMed:2734021). Translocation t(8;10)(p21.3;q11.2) with PCM1 generates the PCM1/RET fusion (PubMed:10980597). Translocation t(6;10)(p21.3;q11.2) with TRIM27/RFP generates the Delta RFP/RET oncogene (PubMed:12787916). Translocation t(1;10)(p13;q11) with TRIM33 generates the TRIM33/RET (PTC7) oncogene (PubMed:10439047). Translocation t(7;10)(q32;q11) with TRIM24/TIF1 generates the TRIM24/RET (PTC6) oncogene (PubMed:10439047). Translocation t(6;10)(p21.3;q11.2) with TRIM27/RFP generates the TRIM27/RET oncogene (PubMed:3037315).

Mutations in RET have been detected in patients with renal agenesis suggesting a possible involvement of this gene in disease pathogenesis.

Post-translational modifications

Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation.

Proteolytically cleaved by caspase-3. The soluble RET kinase fragment is able to induce cell death. The extracellular cell-membrane anchored RET cadherin fragment accelerates cell adhesion in sympathetic neurons.

Sequence Similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family.

Cellular localization

Alternative names

CDHF12, CDHR16, PTC, RET, RET51, Proto-oncogene tyrosine-protein kinase receptor Ret, Cadherin family member 12, Proto-oncogene c-Ret

swissprot:P07949 entrezGene:5573 omim:164761 omim:188830 omim:601984 swissprot:P10644 swissprot:Q13772 entrezGene:8031 entrezGene:5979

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