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FMS-like tyrosine kinase 3 ligand

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(Redirected from Flt3L) Protein-coding gene in the species Homo sapiens
FLT3LG
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1ETE, 3QS7, 3QS9

Identifiers
AliasesFLT3LG, FL, FLT3L, fms related tyrosine kinase 3 ligand, FLG3L, fms related receptor tyrosine kinase 3 ligand
External IDsOMIM: 600007; MGI: 95560; HomoloGene: 48021; GeneCards: FLT3LG; OMA:FLT3LG - orthologs
Gene location (Human)
Chromosome 19 (human)
Chr.Chromosome 19 (human)
Chromosome 19 (human)Genomic location for FLT3LGGenomic location for FLT3LG
Band19q13.33Start49,474,207 bp
End49,486,231 bp
Gene location (Mouse)
Chromosome 7 (mouse)
Chr.Chromosome 7 (mouse)
Chromosome 7 (mouse)Genomic location for FLT3LGGenomic location for FLT3LG
Band7 B3|7 29.14 cMStart45,129,788 bp
End45,136,432 bp
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • granulocyte

  • blood

  • lymph node

  • canal of the cervix

  • appendix

  • ectocervix

  • gastric mucosa

  • vagina

  • body of uterus

  • muscle layer of sigmoid colon
Top expressed in
  • bone marrow

  • spleen

  • granulocyte

  • islet of Langerhans

  • thymus

  • urinary bladder

  • lip

  • esophagus

  • jejunum

  • duodenum
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

2323

14256

Ensembl

ENSG00000090554

ENSMUSG00000110206

UniProt

P49771

P49772

RefSeq (mRNA)

NM_001204502
NM_001204503
NM_001278637
NM_001278638
NM_001459

NM_013520

RefSeq (protein)
NP_001191431
NP_001191432
NP_001265566
NP_001265567
NP_001450

NP_001191431.1

NP_038548
NP_001389760
NP_001389761
NP_001389762
NP_001389763

NP_001389764
NP_001389765
NP_001389766

Location (UCSC)Chr 19: 49.47 – 49.49 MbChr 7: 45.13 – 45.14 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

Fms-related tyrosine kinase 3 ligand (FLT3LG) is a protein which in humans is encoded by the FLT3LG gene.

Flt3 ligand (FL) is a hematopoietic four helical bundle cytokine. It is structurally homologous to stem cell factor (SCF) and colony stimulating factor 1 (CSF-1). In synergy with other growth factors, Flt3 ligand stimulates the proliferation and differentiation of various blood cell progenitors. For example, it is a major growth factor stimulating the growth of dendritic cells.

FLT3L functions as a cytokine and growth factor that increases the number of immune cells (lymphocytes (B cells and T cells)) by activating the hematopoietic progenitors. It acts by binding to and activating FLT3 (CD135) which is found on what (in mice) are called multipotent progenitor (MPP) and common lymphoid progenitor (CLP) cells. It also induces the mobilization of the hematopoietic progenitors and stem cells in vivo which may help the system to kill cancer cells.

FLT3L is crucial for steady-state plasmacytoid dendritic cell (pDC) and classical dendritic cell (cDC) development. A lack of FLT3L results in low levels of dendritic cells.

In parasite clearance

FLT3L and its receptor are involved in the mammalian immune response to malaria. In strains of plasmodium, FLT3L was shown to be released from mast cells and cause the expansion of dendritic cells, leading to the activation of CD8+ T cells. The same paper suggested that FLT3L release was caused by stimulation of mast cells with uric acid, produced from a precursor secreted by the plasmodium parasite. .

In immunotherapy

In situ vaccine (ISV), combining Flt3L, local radiotherapy, and a TLR3 agonist (poly-ICLC), could recruit, antigen-load and activate intratumoral cross-presenting dendritic cells (DCs) in indolent non-Hodgkin’s lymphomas (iNHLs) treatment (clinical trial: NCT01976585). In this study, intratumoral Flt3L was able to (1) induce the accumulation of large numbers of TLR3+ DCs in the tumor and (2) mediate, together with local irradiation, cross-presentation of TAA by DCs in vitro and in vivo.

References

  1. ^ GRCh38: Ensembl release 89: ENSG00000090554Ensembl, May 2017
  2. ^ GRCm38: Ensembl release 89: ENSMUSG00000110206Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: FLT3LG fms-related tyrosine kinase 3 ligand".
  6. Hannum C, Culpepper J, Campbell D, McClanahan T, Zurawski S, Bazan JF, et al. (April 1994). "Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs". Nature. 368 (6472): 643–648. Bibcode:1994Natur.368..643H. doi:10.1038/368643a0. PMID 8145851. S2CID 4309477.
  7. Lyman SD, James L, Escobar S, Downey H, de Vries P, Brasel K, et al. (January 1995). "Identification of soluble and membrane-bound isoforms of the murine flt3 ligand generated by alternative splicing of mRNAs". Oncogene. 10 (1): 149–157. PMID 7824267.
  8. Karsunky H, Merad M, Cozzio A, Weissman IL, Manz MG (July 2003). "Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo". The Journal of Experimental Medicine. 198 (2): 305–313. doi:10.1084/jem.20030323. PMC 2194067. PMID 12874263.
  9. ^ Shortman K, Naik SH (January 2007). "Steady-state and inflammatory dendritic-cell development". Nature Reviews. Immunology. 7 (1): 19–30. doi:10.1038/nri1996. PMID 17170756. S2CID 5616725.
  10. Rahman AH, Aloman C (July 2013). "Dendritic cells and liver fibrosis". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1832 (7): 998–1004. doi:10.1016/j.bbadis.2013.01.005. PMC 3641166. PMID 23313573.
  11. Guermonprez P, Helft J, Claser C, Deroubaix S, Karanje H, Gazumyan A, et al. (June 2013). "Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection". Nature Medicine. 19 (6): 730–738. doi:10.1038/nm.3197. PMC 3914008. PMID 23685841.
  12. Hammerich L, Marron TU, Upadhyay R, Svensson-Arvelund J, Dhainaut M, Hussein S, et al. (May 2019). "Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination". Nature Medicine. 25 (5): 814–824. doi:10.1038/s41591-019-0410-x. PMID 30962585. S2CID 102353110.

Further reading

External links

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PDB gallery
  • 1ete: CRYSTAL STRUCTURE OF THE FLT3 LIGAND 1ete: CRYSTAL STRUCTURE OF THE FLT3 LIGAND
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