Ret 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. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways. Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL. Belongs to the protein kinase superfamily. Tyr protein kinase family. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.10.1; Kinase, protein; Membrane protein, integral; Oncoprotein; Protein kinase, TK; Protein kinase, tyrosine (receptor); Ret family; TK group
Chromosomal Location of Human Ortholog: 10q11.21
Cellular Component:  cytosol; dendrite; early endosome; endosome membrane; integral component of plasma membrane; intracellular membrane-bounded organelle; membrane raft; neuronal cell body; plasma membrane; plasma membrane protein complex; receptor complex
Molecular Function:  ATP binding; calcium ion binding; protein binding; protein tyrosine kinase activity; signaling receptor activity; transmembrane receptor protein tyrosine kinase activity
Biological Process:  activation of MAPK activity; axon guidance; cellular response to retinoic acid; embryonic epithelial tube formation; enteric nervous system development; glial cell-derived neurotrophic factor receptor signaling pathway; homophilic cell adhesion via plasma membrane adhesion molecules; innervation; lymphocyte migration into lymphoid organs; MAPK cascade; membrane protein proteolysis; neural crest cell migration; neuron cell-cell adhesion; neuron maturation; peptidyl-tyrosine phosphorylation; Peyer's patch morphogenesis; positive regulation of cell adhesion mediated by integrin; positive regulation of cell migration; positive regulation of cell size; positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; positive regulation of MAPK cascade; positive regulation of metanephric glomerulus development; positive regulation of neuron maturation; positive regulation of neuron projection development; positive regulation of peptidyl-serine phosphorylation of STAT protein; positive regulation of protein kinase B signaling; positive regulation of transcription, DNA-templated; posterior midgut development; protein phosphorylation; regulation of axonogenesis; regulation of cell adhesion; response to drug; response to pain; retina development in camera-type eye; signal transduction; ureter maturation; ureteric bud development
Disease: Hirschsprung Disease, Susceptibility To, 1; Multiple Endocrine Neoplasia, Type Iia; Multiple Endocrine Neoplasia, Type Iib; Thyroid Carcinoma, Familial Medullary; Thyroid Carcinoma, Papillary
Reference #:  P07949 (UniProtKB)
Alt. Names/Synonyms: Cadherin family member 12; cadherin-related family member 16; CDHF12; CDHR16; Extracellular cell-membrane anchored RET cadherin 120 kDa fragment; HSCR1; MEN2A; MEN2B; MTC1; Proto-oncogene c-Ret; Proto-oncogene tyrosine-protein kinase receptor Ret; PTC; rearranged during transfection; RET; ret proto-oncogene; ret proto-oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease); RET receptor tyrosine kinase; RET transforming sequence; RET-ELE1; RET51; Soluble RET kinase fragment
Gene Symbols: RET
Molecular weight: 124,319 Da
Basal Isoelectric point: 6.17  Predict pI for various phosphorylation states
CST Pathways:  Tyrosine Kinases & Substrates
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Ret

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