Receptor-type tyrosine-protein kinase FLT3
Also known as: CD135, FLK2, FLT3, STK1
Function
Tyrosine-protein kinase that acts as a 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.
Classification
- Family (Pfam)
- PF00047 ig, PF07714 PK_Tyr_Ser-Thr
- InterPro
- Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Immunoglobulin_dom, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 11
- 1RJB X-ray 2.10A
- 3QS7 X-ray 4.30A
- 3QS9 X-ray 7.80A
- 4RT7 X-ray 3.10A
- 4XUF X-ray 3.20A
- 5X02 X-ray 2.40A
- 6IL3 X-ray 2.50A
- 6JQR X-ray 2.20A
- 7QDP X-ray 3.69A
- 7ZV9 X-ray 4.51A
- 8XB1 X-ray 2.85A
A predicted model is available from AlphaFold.
Gene Ontology · 35
- GO:0005788 endoplasmic reticulum lumen
- GO:0010008 endosome membrane
- GO:0005886 plasma membrane
- GO:0043235 receptor complex
- GO:0005524 ATP binding
- GO:0004896 cytokine receptor activity
- GO:0019838 growth factor binding
- GO:0035259 nuclear glucocorticoid receptor binding
- GO:0141038 phosphatidylinositol 3-kinase activator activity
- GO:0004713 protein tyrosine kinase activity
- GO:0044877 protein-containing complex binding
- GO:0004714 transmembrane receptor protein tyrosine kinase activity
- GO:0005021 vascular endothelial growth factor receptor activity
- GO:0030183 B cell differentiation
- GO:0016477 cell migration
- GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
- GO:0071345 cellular response to cytokine stimulus
- GO:0071385 cellular response to glucocorticoid stimulus
- GO:0035726 common myeloid progenitor cell proliferation
- GO:0019221 cytokine-mediated signaling pathway
- GO:0097028 dendritic cell differentiation
- GO:0030097 hemopoiesis
- GO:0001776 leukocyte homeostasis
- GO:0097421 liver regeneration
- GO:0046651 lymphocyte proliferation
- GO:0002318 myeloid progenitor cell differentiation
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0008284 positive regulation of cell population proliferation
- GO:0043406 positive regulation of MAP kinase activity
- GO:0043410 positive regulation of MAPK cascade
- GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
- GO:0002328 pro-B cell differentiation
- GO:0046777 protein autophosphorylation
- GO:0042981 regulation of apoptotic process
Disease associations
- acute myeloid leukemia MONDO:0018874
Drugs targeting this protein · 40
- SORAFENIB TOSYLATE inhibitor
- FORETINIB inhibitor
- TANDUTINIB inhibitor
- FAMITINIB inhibitor
- FEDRATINIB inhibitor
- AS-602868 inhibitor
- SUNITINIB MALATE inhibitor
- SU-014813 inhibitor
- KW-2449 inhibitor
- ZOTIRACICLIB inhibitor
- RG-1530 inhibitor
- CT-1578 inhibitor
- PACRITINIB inhibitor
- AMUVATINIB inhibitor
- QUIZARTINIB DIHYDROCHLORIDE inhibitor
- CRENOLANIB inhibitor
- LINIFANIB inhibitor
- GILTERITINIB FUMARATE inhibitor
- GILTERITINIB inhibitor
- C-1311 inhibitor
- RUSERONTINIB inhibitor
- PEXIDARTINIB inhibitor
- NINGETINIB inhibitor
- PEXIDARTINIB HYDROCHLORIDE inhibitor
- FEDRATINIB HYDROCHLORIDE inhibitor
- FF-10101 inhibitor
- AKN-028 inhibitor
- ENMD-2076 inhibitor
- AT-9283 inhibitor
- PACRITINIB CITRATE inhibitor
- DOVITINIB inhibitor
- ENMD-981693 inhibitor
- XL-999 inhibitor
- 4SC-203 inhibitor
- SUNITINIB inhibitor
- AST-487 inhibitor
- QUIZARTINIB inhibitor
- LESTAURTINIB inhibitor
- CEP-2563 DIHYDROCHLORIDE inhibitor
- MIDOSTAURIN inhibitor
Related proteins · sequence + function similarity
- Receptor-type tyrosine-protein kinase FLT3 0.98
- Macrophage colony-stimulating factor 1 receptor 1 0.83
- Mast/stem cell growth factor receptor Kit 0.83
- Platelet-derived growth factor receptor beta 0.82
- Platelet-derived growth factor receptor beta 0.82
- Macrophage colony-stimulating factor 1 receptor 0.82
- Macrophage colony-stimulating factor 1 receptor 0.81
- Macrophage colony-stimulating factor 1 receptor 0.81
- Mast/stem cell growth factor receptor Kit 0.81
- Mast/stem cell growth factor receptor-related protein Kit 0.81
- Platelet-derived growth factor receptor beta 0.81
- Mast/stem cell growth factor receptor Kit 0.81
Co-cited proteins · studied together in the literature
- CEACAM1-like protein UL7 1 shared papers
- Receptor-type tyrosine-protein kinase FLT3 1 shared papers
- Ubiquitin/ISG15-conjugating enzyme E2 L6 1 shared papers
- Signal transducer and activator of transcription 5A 1 shared papers
- Tyrosine-protein kinase Fes/Fps 1 shared papers
- Mitogen-activated protein kinase 3 3 shared papers
- Mitogen-activated protein kinase 1 3 shared papers
- Tyrosine-protein kinase Fer 1 shared papers
- Signal transducer and activator of transcription 5B 1 shared papers
- RAC-alpha serine/threonine-protein kinase 1 shared papers
- Signal transducer and activator of transcription 5A 2 shared papers
- E3 ubiquitin-protein ligase SIAH1 1 shared papers
Literature · 33 cited papers
- Human Cytomegalovirus Encodes a Novel FLT3 Receptor Ligand Necessary for Hematopoietic Cell Differentiation and Viral Reactivation. MBio · 2018
- Further activation of FLT3 mutants by FLT3 ligand. Oncogene · 2011
- Structural insights into the extracellular assembly of the hematopoietic Flt3 signaling complex. Blood · 2011
- Protein-tyrosine phosphatase DEP-1 controls receptor tyrosine kinase FLT3 signaling. J. Biol. Chem. · 2011
- mTOR signaling is activated by FLT3 kinase and promotes survival of FLT3-mutated acute myeloid leukemia cells. Mol. Cancer · 2010
- Ubiquitin conjugase UBCH8 targets active FMS-like tyrosine kinase 3 for proteasomal degradation. Leukemia · 2010
- FES kinases are required for oncogenic FLT3 signaling. Leukemia · 2010
- Structural and functional alterations of FLT3 in acute myeloid leukemia. Clin. Cancer Res. · 2009
- Oncogenic Flt3 receptors display different specificity and kinetics of autophosphorylation. Exp. Hematol. · 2009
- Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
- DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature · 2008
- Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival. J. Immunol. · 2008
- … and 21 more in the literature graph
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