FMS-like_tyrosine_kinase_3_ligand Knowpia

FLT3LG
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1ETE, 3QS7, 3QS9
Identifiers
Aliases	FLT3LG, FL, FLT3L, fms related tyrosine kinase 3 ligand, FLG3L, fms related receptor tyrosine kinase 3 ligand
External IDs	OMIM: 600007 MGI: 95560 HomoloGene: 48021 GeneCards: FLT3LG
Gene location (Human)
Chr.	Chromosome 19 (human)
End	49,486,231 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	45,136,432 bp
RNA expression pattern
	Top expressed in
	blood; ; lymph node; ; canal of the cervix; ; appendix; ; gastric mucosa; ; vagina; ; subcutaneous adipose tissue; ; spleen; ; right coronary artery; ; tibial nerve;
	Top expressed in
	bone marrow; ; spleen; ; islet of Langerhans; ; thymus; ; urinary bladder; ; lip; ; esophagus; ; jejunum; ; duodenum; ; colon;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	cytokine activity; protein homodimerization activity; receptor tyrosine kinase binding; signaling receptor binding; 1-phosphatidylinositol-3-kinase activity;
Cellular component	integral component of membrane; membrane; intrinsic component of external side of plasma membrane; plasma membrane; cell surface; extracellular region; extracellular space; intracellular anatomical structure;
Biological process	positive regulation of protein phosphorylation; positive regulation of natural killer cell differentiation; lymphocyte differentiation; positive regulation of cell proliferation in bone marrow; negative regulation of apoptotic process in bone marrow cell; positive regulation of myoblast fusion; positive regulation of cell cycle; positive regulation of myoblast differentiation; positive regulation of cell population proliferation; embryonic hemopoiesis; homeostasis of number of cells within a tissue; regulation of myeloid dendritic cell activation; signal transduction; positive regulation of transcription by RNA polymerase II; positive regulation of osteoclast proliferation; regulation of signaling receptor activity; cytokine-mediated signaling pathway; positive regulation of natural killer cell proliferation; MAPK cascade; phosphatidylinositol-3-phosphate biosynthetic process;
	Sources:Amigo / QuickGO
Orthologs
	2323
	14256
	ENSG00000090554
	ENSMUSG00000110206
	P49771
	P49772
	NM_001204502; NM_001204503; NM_001278637; NM_001278638; NM_001459
	NM_013520
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
	Wikidata
View/Edit Human	View/Edit Mouse

Fms-related tyrosine kinase 3 ligand (FLT3LG) is a protein which in humans is encoded by the FLT3LG gene.^[5]^[6]^[7]

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.^[8]

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.^[9]

FLT3L is crucial for steady-state plasmacytoid dendritic cell (pDC) and classical dendritic cell (cDC) development.^[9]^[10] A lack of FLT3L results in low levels of dendritic cells.

In parasite clearance edit

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. .^[11]

In immunotherapy edit

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).^[12] 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 edit

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000090554 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000110206 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: FLT3LG fms-related tyrosine kinase 3 ligand".
^ 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.
^ 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.
^ 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.

External links edit

FLT3 signaling

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000090554 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000110206 – Ensembl, 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.

[entrez-5] "Entrez Gene: FLT3LG fms-related tyrosine kinase 3 ligand".

[pmid8145851-6] 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.

[pmid7824267-7] 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.

[Shortman2006-9] 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.

[Rahman2013-10] 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.

[Guermonprez2013-11] 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.

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Summary

In parasite clearance edit

In immunotherapy edit

References edit

Further reading edit

External links edit