Molecule Information

General Information of the Molecule (ID: Mol04364)

• Name: Receptor-type tyrosine-protein kinase FLT3 (FLT3) ,Homo sapiens
• Synonyms: FL cytokine receptor; Fetal liver kinase-2; Fms-like tyrosine kinase 3; Stem cell tyrosine kinase 1; CD_antigen=CD135
• Molecule Type: Protein
• Gene Name: FLT3
• Gene ID: 2322
• Sequence:
  MPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKSSSYPMVSESP
  EDLGCALRPQSSGTVYEAAAVEVDVSASITLQVLVDAPGNISCLWVFKHSSLNCQPHFD
  L QNRGVVSMVILKMTETQAGEYLLFIQSEATNYTILFTVSIRNTLLYTLRRPYFRKMEN
  QD ALVCISESVPEPIVEWVLCDSQGESCKEESPAVVKKEEKVLHELFGTDIRCCARNEL
  GRE CTRLFTIDLNQTPQTTLPQLFLKVGEPLWIRCKAVHVNHGFGLTWELENKALEEGN
  YFEM STYSTNRTMIRILFAFVSSVARNDTGYYTCSSSKHPSQSALVTIVEKGFINATNS
  SEDYE IDQYEEFCFSVRFKAYPQIRCTWTFSRKSFPCEQKGLDNGYSISKFCNHKHQPG
  EYIFHA ENDDAQFTKMFTLNIRRKPQVLAEASASQASCFSDGYPLPSWTWKKCSDKSPN
  CTEEITE GVWNRKANRKVFGQWVSSSTLNMSEAIKGFLVKCCAYNSLGTSCETILLNSP
  GPFPFIQD NISFYATIGVCLLFIVVLTLLICHKYKKQFRYESQLQMVQVTGSSDNEYFY
  VDFREYEYD LKWEFPRENLEFGKVLGSGAFGKVMNATAYGISKTGVSIQVAVKMLKEKA
  DSSEREALMS ELKMMTQLGSHENIVNLLGACTLSGPIYLIFEYCCYGDLLNYLRSKREK
  FHRTWTEIFKE HNFSFYPTFQSHPNSSMPGSREVQIHPDSDQISGLHGNSFHSEDEIEY
  ENQKRLEEEEDL NVLTFEDLLCFAYQVAKGMEFLEFKSCVHRDLAARNVLVTHGKVVKI
  CDFGLARDIMSDS NYVVRGNARLPVKWMAPESLFEGIYTIKSDVWSYGILLWEIFSLGV
  NPYPGIPVDANFYK LIQNGFKMDQPFYATEEIYIIMQSCWAFDSRKRPSFPNLTSFLGC
  QLADAEEAMYQNVDG RVSECPHTYQNRRPFSREMDLGLLSPQAQVEDS
• Function: Tyrosine-protein kinase that acts as a cell-surface receptorfor the cytokine FLT3LG and regulates differentiation, proliferationand survival of hematopoietic progenitor cells and of dendritic cells.Promotes phosphorylation of SHC1 and AKT1, and activation of thedownstream effector MTOR. Promotes activation of RAS signaling andphosphorylation of downstream kinases, including MAPK1/ERK2 and/orMAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP,PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-typeFLT3 causes only marginal activation of STAT5A or STAT5B. Mutationsthat cause constitutive kinase activity promote cell proliferation andresistance to apoptosis via the activation of multiple signalingpathways. {ECO:0000269|PubMed:10080542, ECO:0000269|PubMed:11090077,ECO:0000269|PubMed:14504097, ECO:0000269|PubMed:16266983,ECO:0000269|PubMed:16627759, ECO:0000269|PubMed:18490735,ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:21067588,ECO:0000269|PubMed:21262971, ECO:0000269|PubMed:21516120,ECO:0000269|PubMed:7507245}.
• Uniprot ID: FLT3_HUMAN
• Ensembl ID: ENSG0000012202515
• HGNC ID: HGNC:3765

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Sorafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] [1]

• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Resistant Drug: Sorafenib
• Molecule Alteration: Mutation; D1194A
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FLT3-ITD signalling pathway; Regulation; N.A.
• In Vitro Model: MOLM-13/sor cells; Blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: WES assay
• Experiment for Drug Resistance: Apoptosis assay
• Mechanism Description: Sorafenib-resistant MOLM-13/sor cells have increased protein levels of FLT3 and Axl signaling pathways. These results suggest that activated FLT3-ITD signaling, Axl signaling, and protein translation contribute to sorafenib resistance.

Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] [1]

• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Resistant Drug: Sorafenib
• Molecule Alteration: Mutation; Rv1173; c.-32 A?>?G
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FLT3-ITD signalling pathway; Regulation; N.A.
• In Vitro Model: MOLM-13/sor cells; Blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: WES assay
• Experiment for Drug Resistance: Apoptosis assay
• Mechanism Description: Sorafenib-resistant MOLM-13/sor cells have increased protein levels of FLT3 and Axl signaling pathways. These results suggest that activated FLT3-ITD signaling, Axl signaling, and protein translation contribute to sorafenib resistance.

References

• Ref 1: The GSK3beta/Mcl-1 axis is regulated by both FLT3-ITD and Axl and determines the apoptosis induction abilities of FLT3-ITD inhibitors. Cell Death Discov. 2023 Feb 4;9(1):44.