RET - Proto-oncogene tyrosine-protein kinase receptor Ret - human protein (Function)
 
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RET »  Proto-oncogene tyrosine-protein kinase receptor Ret   [ EC 2.7.10.1 ]
 
Protein also known as:  Cadherin family member 12. Cleaved into:  Extracellular cell-membrane anchored RET cadherin 120 kDa fragment; Soluble RET kinase fragment.
Gene name:  RET
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

 show evidences
Overview 
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; 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. 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. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; 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. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration.  
6
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Calcium ion bindingdefinition[GO:0005509]  
1
  • FlyBase
Protein bindingdefinition[GO:0005515]  
6
  • IntAct
  • UniProtKB
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • PINC
Receptor activitydefinition[GO:0004872]  
1
  • PINC
Transmembrane receptor protein tyrosine kinase activitydefinition[GO:0004714]  
1
  • EC 2 GO
GO biological process 
Isoform  Iso 2   Activation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0006919]  
1
  • UniProtKB
Cellular response to retinoic aciddefinition[GO:0071300]  
1
  • BHF-UCL
Embryonic epithelial tube formationdefinition[GO:0001838] silver  
1
  • Ortholog Compara
Enteric nervous system developmentdefinition[GO:0048484] silver  
1
  • Ortholog Compara
Homophilic cell adhesion via plasma membrane adhesion moleculesdefinition[GO:0007156] silver  
1
  • InterPro 2 GO
Innervationdefinition[GO:0060384] silver  
1
  • Ortholog Compara
Lymphocyte migration into lymphoid organsdefinition[GO:0097021]  
1
  • Ortholog Curator
MAPK cascadedefinition[GO:0000165] silver  
1
  • Ortholog Compara
Membrane protein proteolysisdefinition[GO:0033619]  
1
  • UniProtKB
Neural crest cell migrationdefinition[GO:0001755] silver  
1
  • Ortholog Compara
Neuron cell-cell adhesiondefinition[GO:0007158]  
1
  • UniProtKB
Neuron maturationdefinition[GO:0042551] silver  
1
  • Ortholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
4
  • GOC
  • EC 2 GO
  • InterPro 2 GO
  • UniProtKB KW
Peyer's patch morphogenesisdefinition[GO:0061146]  
1
  • Ortholog Curator
Positive regulation of cell adhesion mediated by integrindefinition[GO:0033630]  
1
  • UniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
1
  • UniProtKB
Positive regulation of cell sizedefinition[GO:0045793] silver  
1
  • Ortholog Compara
Positive regulation of extrinsic apoptotic signaling pathway in absence of liganddefinition[GO:2001241]  
2
  • UniProtKB
Positive regulation of metanephric glomerulus developmentdefinition[GO:0072300]  
1
  • UniProtKB
Positive regulation of neuron maturationdefinition[GO:0014042] silver  
1
  • Ortholog Compara
Positive regulation of neuron projection developmentdefinition[GO:0010976]  
1
  • BHF-UCL
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
1
  • UniProtKB
Posterior midgut developmentdefinition[GO:0007497]  
1
  • PINC
Protein phosphorylationdefinition[GO:0006468]  
1
  • PINC
Regulation of axonogenesisdefinition[GO:0050770] silver  
1
  • Ortholog Compara
Regulation of cell adhesiondefinition[GO:0030155]  
1
  • UniProtKB
Response to drugdefinition[GO:0042493] silver  
1
  • Ortholog Compara
Response to paindefinition[GO:0048265]  
1
  • Ortholog Curator
Retina development in camera-type eyedefinition[GO:0060041] silver  
1
  • Ortholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • PINC
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169] silver  
1
  • Ortholog Compara
Ureter maturationdefinition[GO:0035799] silver  
1
  • Ortholog Compara
Ureteric bud developmentdefinition[GO:0001657] silver  
1
  • Ortholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
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  • PROSITE-ProRule
  • UniProtKB
It is regulated in the following manner
Repressed by 4-(3-hydroxyanilino)-quinolines derivatives, indolin-2-one-derivatives, 2-(alkylsulfanyl)-4-(3-thienyl) nicotinonitrile analogs, 3- and 4-substituted beta-carbolin-1-ones, vandetanib, motesanib, sorafenib (BAY 43-9006), cabozantinib (XL184), sunitinib, and withaferin A (WA). Inactivation by sorafenib both reduces kinase activity and promotes lysosomal degradation.  
8
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Endocytosis  hsa04144+5979  
Pathways in cancer  hsa05200+5979  
Thyroid cancer  hsa05216+5979  
Note 
Treatment with withaferin A (WA) leads tumor regression in medullary thyroid carcinomas (MTC).  
1
  • UniProtKB
 

Keywords

Biological process 
Cell adhesion  definition   [KW-0130]
Molecular function 
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: RET_proto-oncogene
GenomeRNAi: 5979
PRO: PR:P07949
Chemistry
GuidetoPHARMACOLOGY: 2185