Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10141)
Regulator Name Receptor-type tyrosine-protein kinase FLT3 (FLT3)
Synonyms
CD135, FLK2, STK1; FL cytokine receptor; Fetal liver kinase-2; Fms-like tyrosine kinase 3; Stem cell tyrosine kinase 1; CD_antigen=CD135
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Gene Name FLT3
Gene ID 2322
Regulator Type Protein coding
Uniprot ID P36888
Sequence
MPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKSSSYPMVSESP
EDLGCALRPQSSGTVYEAAAVEVDVSASITLQVLVDAPGNISCLWVFKHSSLNCQPHFDL
QNRGVVSMVILKMTETQAGEYLLFIQSEATNYTILFTVSIRNTLLYTLRRPYFRKMENQD
ALVCISESVPEPIVEWVLCDSQGESCKEESPAVVKKEEKVLHELFGTDIRCCARNELGRE
CTRLFTIDLNQTPQTTLPQLFLKVGEPLWIRCKAVHVNHGFGLTWELENKALEEGNYFEM
STYSTNRTMIRILFAFVSSVARNDTGYYTCSSSKHPSQSALVTIVEKGFINATNSSEDYE
IDQYEEFCFSVRFKAYPQIRCTWTFSRKSFPCEQKGLDNGYSISKFCNHKHQPGEYIFHA
ENDDAQFTKMFTLNIRRKPQVLAEASASQASCFSDGYPLPSWTWKKCSDKSPNCTEEITE
GVWNRKANRKVFGQWVSSSTLNMSEAIKGFLVKCCAYNSLGTSCETILLNSPGPFPFIQD
NISFYATIGVCLLFIVVLTLLICHKYKKQFRYESQLQMVQVTGSSDNEYFYVDFREYEYD
LKWEFPRENLEFGKVLGSGAFGKVMNATAYGISKTGVSIQVAVKMLKEKADSSEREALMS
ELKMMTQLGSHENIVNLLGACTLSGPIYLIFEYCCYGDLLNYLRSKREKFHRTWTEIFKE
HNFSFYPTFQSHPNSSMPGSREVQIHPDSDQISGLHGNSFHSEDEIEYENQKRLEEEEDL
NVLTFEDLLCFAYQVAKGMEFLEFKSCVHRDLAARNVLVTHGKVVKICDFGLARDIMSDS
NYVVRGNARLPVKWMAPESLFEGIYTIKSDVWSYGILLWEIFSLGVNPYPGIPVDANFYK
LIQNGFKMDQPFYATEEIYIIMQSCWAFDSRKRPSFPNLTSFLGCQLADAEEAMYQNVDG
RVSECPHTYQNRRPFSREMDLGLLSPQAQVEDS

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Family Tyr protein kinase family
Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.

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HGNC ID
HGNC:3765
KEGG ID hsa:2322
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
FLT3 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
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Browse Disease
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Nervous system disease ICD-11: 8E7Z
 Disease Info 
Pathway Response Ferroptosis hsa04216
Apoptosis hsa04210
Necroptosis hsa04217
Citrate cycle hsa00020
Cell Process Cell ferroptosis
Cell apoptosis
Cell necrosis
In Vitro Model
 HT22 cells Normal Mus musculus CVCL_0321
661W cells Normal Mus musculus CVCL_6240
RGC-5 cells Normal Mus musculus CVCL_4059
C6 cells Malignant glioma Rattus norvegicus CVCL_0194
In Vivo Model
Whole cerebral neocortices were removed from the rat fetuses, and incubated in 0.03% trypsin in Earles balanced salt solution (EBSS) without Ca2 + or Mg2 + for 90 min at 37. Subsequently, the cortices washed with fresh EBSS, transferred into culture medium (12.5% F-12 growth media (Sigma), 12.5% heat inactivated horse serum (Hyclone), 30 U/ml Penicillin, 0.03 mg/ml Streptomycin solution (both Sigma), 2.5 mM glutamine (Sigma), 10 mM HEPES (Omega) in DMEM with high glucose (4500 g/l, Sigma) and dissociated by trituration.

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Response regulation Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases. The PI3K (PIK3CA) inhibitor protects cells by inducing partial restoration of depleted glutathione levels and accumulation of intracellular amino acids, whereas the Flt3 inhibitor prevents lipid peroxidation, a key mechanism of glutamate-mediated toxicity.
Nervous system disease [ICD-11: 8E7Z]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Receptor-type tyrosine-protein kinase FLT3 (FLT3) Protein coding
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Apoptosis hsa04210
Necroptosis hsa04217
Citrate cycle hsa00020
Cell Process Cell ferroptosis
Cell apoptosis
Cell necrosis
In Vitro Model
 HT22 cells Normal Mus musculus CVCL_0321
661W cells Normal Mus musculus CVCL_6240
RGC-5 cells Normal Mus musculus CVCL_4059
C6 cells Malignant glioma Rattus norvegicus CVCL_0194
In Vivo Model
Whole cerebral neocortices were removed from the rat fetuses, and incubated in 0.03% trypsin in Earles balanced salt solution (EBSS) without Ca2 + or Mg2 + for 90 min at 37. Subsequently, the cortices washed with fresh EBSS, transferred into culture medium (12.5% F-12 growth media (Sigma), 12.5% heat inactivated horse serum (Hyclone), 30 U/ml Penicillin, 0.03 mg/ml Streptomycin solution (both Sigma), 2.5 mM glutamine (Sigma), 10 mM HEPES (Omega) in DMEM with high glucose (4500 g/l, Sigma) and dissociated by trituration.

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Response regulation Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases. The PI3K (PIK3CA) inhibitor protects cells by inducing partial restoration of depleted glutathione levels and accumulation of intracellular amino acids, whereas the Flt3 inhibitor prevents lipid peroxidation, a key mechanism of glutamate-mediated toxicity.
References
Ref 1 Cellular protection using Flt3 and PI3K inhibitors demonstrates multiple mechanisms of oxidative glutamate toxicity. Nat Commun. 2014 Apr 17;5:3672. doi: 10.1038/ncomms4672.