Fms-like tyrosine kinase 3

Fms様チロシンキナーゼ3

WordNet

1. want to have; "Id like a beer now!"
2. a kind of person; "Well not see his like again"; "I cant tolerate people of his ilk" (同)ilk
3. a similar kind; "dogs, foxes, and the like", "we dont want the likes of you around here" (同)the like, the likes of
4. equal in amount or value; "like amounts"; "equivalent amounts"; "the same amount"; "gave one six blows and the other a like number"; "the same number" (同)same
5. resembling or similar; having the same or some of the same characteristics; often used in combination; "suits of like design"; "a limited circle of like minds"; "members of the cat family have like dispositions"; "as like as two peas in a pod"; "doglike devotion"; "a dreamlike quality" (同)similar
6. be fond of; "I like my nephews"
7. feel about or towards; consider, evaluate, or regard; "How did you like the Presidents speech last night?"
8. find enjoyable or agreeable; "I like jogging"; "She likes to read Russian novels"
9. a feeling of pleasure and enjoyment; "Ive always had a liking for reading"; "she developed a liking for gin"
10. an enzyme that catalyzes the conversion of a proenzyme to an active enzyme
11. the 6th letter of the Roman alphabet (同)f
12. an amino acid found in most proteins; a precursor of several hormones

PrepTutorEJDIC

1. …‘を'『好む』,‘が'好きである / 《しばしば否定文で,またwould,《英》shouldと共に用いて》…‘を'望む,…したい / 『好む』;望む / 《複数形で》好み,好きな事
2. (外観・性質などが)…『に似た』,のような / (やり方,程度などが)…『と同じように』 / …『らしい』,にふさわいし / 《おもに話》たとえば…のような / 《名詞の前にのみ用いて》(性質・外観などが)同じの,(数量が)等しい / 《補語にのみ用いて》似ている,そっくりで / たぶん,おそらく(probably) / (…に)似た人(物),(…と)同等の人(物),匹敵する人(物)《+『of』+『名』》 / …のように / あたかも…のように
3. (…の)『好み』,趣味《+『for』(『to』)+『名』》

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/07/08 04:07:06」(JST)

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FLT3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1RJB, 3QS7, 3QS9, 4RT7, 4XUF
Identifiers
Aliases	FLT3, CD135, FLK-2, FLK2, STK1, fms related tyrosine kinase 3
External IDs	OMIM: 136351 MGI: 95559 HomoloGene: 3040 GeneCards: FLT3
Gene ontology Molecular function • vascular endothelial growth factor-activated receptor activity • nucleotide binding • protein kinase activity • transferase activity • protein homodimerization activity • protein complex binding • kinase activity • protein binding • glucocorticoid receptor binding • cytokine receptor activity • transmembrane receptor protein tyrosine kinase activity • protein tyrosine kinase activity • ATP binding • protein self-association Cellular component • cytoplasm • integral component of membrane • cytosol • endoplasmic reticulum lumen • membrane • integral component of plasma membrane • protein complex • nucleus • plasma membrane • endoplasmic reticulum Biological process • leukocyte homeostasis • regulation of apoptotic process • dendritic cell differentiation • hemopoiesis • cell differentiation • myeloid progenitor cell differentiation • positive regulation of MAP kinase activity • phosphorylation • transmembrane receptor protein tyrosine kinase signaling pathway • cytokine-mediated signaling pathway • common myeloid progenitor cell proliferation • positive regulation of tyrosine phosphorylation of STAT protein • cellular response to cytokine stimulus • positive regulation of phosphatidylinositol 3-kinase activity • protein phosphorylation • pro-B cell differentiation • cellular response to glucocorticoid stimulus • animal organ regeneration • response to organonitrogen compound • positive regulation of cell proliferation • lymphocyte proliferation • protein autophosphorylation • positive regulation of phosphatidylinositol 3-kinase signaling • peptidyl-tyrosine phosphorylation • B cell differentiation • positive regulation of MAPK cascade • vascular endothelial growth factor signaling pathway Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2322	14255
Ensembl	ENSG00000122025	ENSMUSG00000042817
UniProt	P36888	Q00342
RefSeq (mRNA)	NM_004119	NM_010229
RefSeq (protein)	NP_004110	NP_034359
Location (UCSC)	Chr 13: 28 – 28.1 Mb	Chr 5: 147.33 – 147.4 Mb
PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3 (FLT-3), receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the FLT3 gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L).

It is expressed on the surface of many hematopoietic progenitor cells. Signalling of FLT3 is important for the normal development of haematopoietic stem cells and progenitor cells.

The FLT3 gene is one of the most frequently mutated genes in acute myeloid leukemia (AML). High levels of wild-type FLT3 have been reported for blast cells of some AML patients without FLT3 mutations. These high levels may be associated with worse prognosis.

Structure

FLT3 is composed of five extracellular immunoglobulin-like domains, an extracellular domain, a transmembrane domain, a juxtamembrane domain and a tyrosine-kinase domain consisting of 2 lobes that are connected by a tyrosine-kinase insert. Cytoplasmic FLT3 undergoes glycosylation, which promotes localization of the receptor to the membrane.

Function

CD135 is a Class III receptor tyrosine kinase. When this receptor binds to FLT3L a ternary complex is formed in which two FLT3 molecules are bridged by one (homodimeric) FLT3L. The formation of such complex brings the two intracellular domains in close proximity to each other, eliciting initial trans-phosphorylation of each kinase domain. This initial phosphorylation event further activates the intrinsic tyrosine kinase activity, which in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. 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).

Two cytokines that down modulate FLT3 activity (& block FLT3-induced hematopoietic activity) are:

• TNF-Alpha (Tumor necrosis factor-alpha)
• TGF-Beta (Transforming growth factor-beta)

TGF-Beta especially, decreases FLT3 protein levels and reverses the FLT3L-induced decrease in the time that hematopoietic progenitors spend in the G1-phase of the cell cycle.

Clinical significance

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) express 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. (See Lymphopoiesis#Labeling lymphopoiesis)

Role in cancer

CD135 is a proto-oncogene, meaning that mutations of this protein can lead to cancer. 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 prognostic indicator associated with adverse disease outcome.

FLT3 inhibitors

Quizartinib (AC220) and midostaurin were in phase II clinical trials for AML patients with FLT3 mutations. Quizartinib had good results in a phase II clinical trial for refractory AML - particularly in patients who went on to have a stem cell transplant.

Sorafenib has been reported to show significant activity against Flt3-ITD positive acute myelogenous leukemia.

Sunitinib also inhibits Flt3.

Lestaurtinib is in clinical trials.

A paper published in Nature in April 2012 studied patients who developed resistance to FLT3 inhibitors, finding specific DNA sites contributing to that resistance and highlighting opportunities for future development of inhibitors that could take into account the resistance-conferring mutations for a more potent treatment.

See also

• Cluster of differentiation
• cytokine receptor
• receptor tyrosine kinase
• tyrosine kinase
• oncogene
• hematopoiesis
• Lymphopoiesis#Labeling lymphopoiesis

Further reading

• Masson K, Rönnstrand L (2009). "Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3.". Cell. Signal. 21 (12): 1717–1726. PMID 19540337. doi:10.1016/j.cellsig.2009.06.002. 
• Reilly JT (2003). "FLT3 and its role in the pathogenesis of acute myeloid leukaemia.". Leuk. Lymphoma. 44 (1): 1–7. PMID 12691136. doi:10.1080/1042819021000040233. 
• 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. doi:10.1080/1042819031000067503. 
• 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. doi:10.1016/S1521-6926(03)00063-X. 
• Drexler HG, Quentmeier H (2005). "FLT3: receptor and ligand.". Growth Factors. 22 (2): 71–3. PMID 15253381. doi:10.1080/08977190410001700989. 
• Naoe T, Kiyoi H (2005). "Normal and oncogenic FLT3.". Cell. Mol. Life Sci. 61 (23): 2932–8. PMID 15583855. doi:10.1007/s00018-004-4274-x. 
• 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. doi:10.1097/01.moh.0000147891.06584.d7. 
• 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. doi:10.1097/01.moh.0000149608.29685.d1. 
• 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. PMID 15778081. doi:10.1016/j.biocel.2004.12.005. 
• Zheng R, Small D (2006). "Mutant FLT3 signaling contributes to a block in myeloid differentiation.". Leuk. Lymphoma. 46 (12): 1679–87. PMID 16263569. doi:10.1080/10428190500261740. 
• 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. PMID 16410383. doi:10.1634/stemcells.2005-0519. 
• Stubbs MC, Armstrong SA (2007). "FLT3 as a therapeutic target in childhood acute leukemia.". Current drug targets. 8 (6): 703–14. PMID 17584026. doi:10.2174/138945007780830782. 

External links

• CD135 Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human FLT3 genome location and FLT3 gene details page in the UCSC Genome Browser.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 急性骨髄性白血病の予後 prognosis of acute myeloid leukemia
• 2. 血管新生阻害剤の概要 overview of angiogenesis inhibitors
• 3. 急性骨髄性白血病の臨床症状、病理学的特徴、および診断 clinical manifestations pathologic features and diagnosis of acute myeloid leukemia
• 4. 慢性骨髄性白血病の治療の概要 overview of the treatment of chronic myeloid leukemia
• 5. 小児および思春期における急性骨髄性白血病 acute myeloid leukemia in children and adolescents

English Journal

• Analysis of class I and II aberrations in Iraqi childhood acute myeloid leukemia using filter paper cards.

• Al-Kzayer LF1, Uyen le TN, Al-Jadiry MF, Al-Hadad SA, Al-Badri SA, Ghali HH, Ameen NA, Liu T, Matsuda K, Abdulkadhim JM, Al-Shujairi TA, Matti ZI, Hasan JG, Al-Abdullah HM, Al-Ani MH, Saber PA, Khalil HM, Inoshita T, Kamata M, Koike K, Sakashita K.
• Annals of hematology.Ann Hematol.2014 Jun;93(6):949-55. doi: 10.1007/s00277-014-2007-2. Epub 2014 Jan 25.
• The lack of molecular diagnosis in the field of cancer in Iraq has motivated us to perform a genetic analysis of pediatric acute myelogenous leukemia (AML), including class I and II aberrations. Peripheral blood or bone marrow cells were collected from 134 AML children aged ≤15 years. Flinders Te
• PMID 24464319

• Role of CD8+ T cells and myeloid DCs in protection from ocular HSV-1 challenge in immunized mice.

• Matundan H1, Mott KR, Ghiasi H.
• Journal of virology.J Virol.2014 May 7. [Epub ahead of print]
• The development of immunization strategies to protect against ocular infection with herpes simplex virus-1 (HSV-1) must address the issue of the effects of the strategy on the establishment of latency in the trigeminal ganglia (TG). It is the reactivation of this latent virus that can cause recurren
• PMID 24807710

• Reversal of Acquired Drug Resistance in FLT3-Mutated Acute Myeloid Leukemia Cells via Distinct Drug Combination Strategies.

• Zhang W1, Gao C, Konopleva M, Chen Y, Jacamo RO, Borthakur G, Cortes JE, Ravandi F, Ramachandran A, Andreeff M.
• Clinical cancer research : an official journal of the American Association for Cancer Research.Clin Cancer Res.2014 May 1;20(9):2363-74. doi: 10.1158/1078-0432.CCR-13-2052. Epub 2014 Mar 11.
• PURPOSE: FMS-like tyrosine kinase-3 (FLT3) internal tandem duplication (FLT3-ITD) mutations are common in patients with acute myeloid leukemia (AML). These patients regularly develop resistance to FLT3 inhibitors suggesting that targeted combination drug strategies are needed to enhance AML therapy
• PMID 24619500

Japanese Journal

• A neutral lipid envelope-type nanoparticle composed of a pH-activated and vitamin E-scaffold lipid-like material as a platform for a gene carrier targeting renal cell carcinoma

• Journal of controlled release 200, 97-105, 2015-02-28
• NAID 120005567732

• Serum concentrations of Flt-3 ligand in rheumatic diseases

• BioScience Trends 9(5), 342-349, 2015
• NAID 130005109609

• Is thrombin a "toxin" in the pathogenesis of preeclampsia?

• Hypertension Research in Pregnancy 3(1), 13-18, 2015
• NAID 130005093543

Related Links

• FLT3 (FMS-like tyrosine kinase 3) - Atlas of Genetics and ...

FLT3 (FMS-like tyrosine kinase 3), Authors: Olivier Rosnet. Published in: Atlas Genet Cytogenet Oncol Haematol. ... Somatic Mutations in the FLT3 gene are the most frequent genetic aberration that have been described in acute ...

• Leukemia - Targeting the FMS-like tyrosine kinase 3 in ...

Top of page Abstract Acute myeloid leukemia (AML) is a highly heterogenous disease with multiple signaling pathways contributing to its pathogenesis. A key driver of AML is the FMS-like tyrosine kinase receptor-3 ...

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★リンクテーブル★

リンク元	「Fms様チロシンキナーゼ3」
関連記事	「like」「kinase」「FMS」「F」「Fm」

「Fms様チロシンキナーゼ3」

　　[★]

英

Fms-like tyrosine kinase 3

「like」

　　[★]

• v.

• 好む

• prep.

• 似ている、同様の

関

alike、as well as、care for、correspond、correspondingly、equally、favor、identically、likewise、prefer、resemble、same、similar、similarly、such

　 　 　 　 　 　 　 　 　 　

「kinase」

　　[★] キナーゼ カイネース リン酸化酵素 phosphoenzyme phosphotransferase 　

「FMS」

　　[★] 線維性筋痛症候群 fibromyalgia syndrome

「F」

　　[★] フェニルアラニン phenylalanine 　

「Fm」

　　[★]

フェルミウム

関

fermium