Fms-related tyrosine kinase 3
|
Identifiers
|
Symbol(s)
| FLT3; STK1; CD135; FLK2
|
External IDs
| OMIM: 136351 MGI: 95559 Homologene: 3040
|
Gene Ontology
|
Molecular Function:
| • nucleotide binding • receptor activity • vascular endothelial growth factor receptor activity • ATP binding • transferase activity
|
Cellular Component:
| • integral to plasma membrane • membrane
|
Biological Process:
| • protein amino acid phosphorylation • transmembrane receptor protein tyrosine kinase signaling pathway • positive regulation of cell proliferation
|
|
RNA expression pattern
|
More reference expression data
|
Orthologs
|
| Human
| Mouse
|
Entrez
| 2322
| 14255
|
Ensembl
| ENSG00000122025
| ENSMUSG00000042817
|
Uniprot
| P36888
| Q2VPD1
|
Refseq
| NM_004119 (mRNA) NP_004110 (protein)
| NM_010229 (mRNA) NP_034359 (protein)
|
Location
| Chr 13: 27.48 - 27.57 Mb
| Chr 5: 147.64 - 147.71 Mb
|
Pubmed search
| [1]
| [2]
|
CD135 is a cytokine receptor expressed on the surface of hematopoietic progenitor cells.
Additional recommended knowledge
Synonyms
fms-like tyrosine kinase receptor-3 (Flt3), fetal liver kinase-2 (Flk2)
Cell Surface Marker
Cluster of differentiation (CD) molecules are markers on the cell surface, as recognized by specific sets of antibodies, used to identify the cell type, stage of differentiation and activity of a cell. CD135 is an important cell surface marker used to identify certain types of hematopoietic (blood) progenitors in the bone marrow. Specifically, multipotent progenitors (MPP) and common lymphoid progenitors (CLP) expresse high surface levels of CD135. This marker is therefore used to differentiate hematopoietic stem cells (HSC), which are CD135 negative, from MPPs, which are CD135 positive.
Ligand
CD135 is the receptor for the cytokine Flt3 ligand (Flt3L).
Function
CD135 is a receptor tyrosine kinase type III. When this receptor binds to Flt3L it forms a dimer with itself (homodimer) which activates signaling through second messengers. Signaling through CD135 plays a role in cell survival, proliferation, and differentiation. CD135 is important for lymphocyte (B cell and T cell) development, but not for the development of other blood cells (myeloid development).
Role in cancer
CD135 is a proto-oncogene, meaning that mutations of this protein can lead to cancer[1]. Mutations of the Flt3 receptor can lead to the development of leukemia, a cancer of bone marrow hematopoietic progenitors. Internal tandem duplications of Flt3 (Flt3-ITD) are the most common mutations associated with acute myelogenous leukemia (AML) and are a poor prognostic indicator.
See also
References
- ^ http://AtlasGeneticsOncology.org/Genes/FLT3ID144.html
Further reading
- Reilly JT (2003). "FLT3 and its role in the pathogenesis of acute myeloid leukaemia.". Leuk. Lymphoma 44 (1): 1-7. PMID 12691136.
- Kottaridis PD, Gale RE, Linch DC (2003). "Prognostic implications of the presence of FLT3 mutations in patients with acute myeloid leukemia.". Leuk. Lymphoma 44 (6): 905-13. PMID 12854887.
- Gilliland DG (2004). "FLT3-activating mutations in acute promyelocytic leukaemia: a rationale for risk-adapted therapy with FLT3 inhibitors.". Best practice & research. Clinical haematology 16 (3): 409-17. PMID 12935959.
- Drexler HG, Quentmeier H (2005). "FLT3: receptor and ligand.". Growth Factors 22 (2): 71-3. PMID 15253381.
- Naoe T, Kiyoi H (2005). "Normal and oncogenic FLT3.". Cell. Mol. Life Sci. 61 (23): 2932-8. doi:10.1007/s00018-004-4274-x. PMID 15583855.
- Sternberg DW, Licht JD (2005). "Therapeutic intervention in leukemias that express the activated fms-like tyrosine kinase 3 (FLT3): opportunities and challenges.". Curr. Opin. Hematol. 12 (1): 7-13. PMID 15604885.
- Marcucci G, Mrózek K, Bloomfield CD (2005). "Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics.". Curr. Opin. Hematol. 12 (1): 68-75. PMID 15604894.
- Markovic A, MacKenzie KL, Lock RB (2005). "FLT-3: a new focus in the understanding of acute leukemia.". Int. J. Biochem. Cell Biol. 37 (6): 1168-72. doi:10.1016/j.biocel.2004.12.005. PMID 15778081.
- Zheng R, Small D (2006). "Mutant FLT3 signaling contributes to a block in myeloid differentiation.". Leuk. Lymphoma 46 (12): 1679-87. doi:10.1080/10428190500261740. PMID 16263569.
- Parcells BW, Ikeda AK, Simms-Waldrip T, et al. (2007). "FMS-like tyrosine kinase 3 in normal hematopoiesis and acute myeloid leukemia.". Stem Cells 24 (5): 1174-84. doi:10.1634/stemcells.2005-0519. PMID 16410383.
- Stubbs MC, Armstrong SA (2007). "FLT3 as a therapeutic target in childhood acute leukemia.". Current drug targets 8 (6): 703-14. PMID 17584026.
|