Flt3l

What is flt3l protein?

FLT3L is a disulfide-linked homodimer, with each monomer composed of 308 amino acids. It belongs to the platelet-derived growth factor/vascular endothelial growth factor family of cytokines. Binds to and signals through FLT3 (Fms-like tyrosine kinase 3) receptor expressed on hematopoietic stem/progenitor cells. Produced by stromal cells, dendritic cells, endothelial cells in bone marrow and lymph nodes.

What is the function of flt3l protein?

Hematopoiesis regulation: Stimulates the proliferation and differentiation of hematopoietic stem cells and progenitors of myeloid and lymphoid lineages.

Dendritic cell development: Plays a critical role in the differentiation and survival of dendritic cell progenitors in the bone marrow and periphery.

B cell production: Promotes the development and expansion of B cell progenitors in the bone marrow.

Natural killer cell development: Involved in the differentiation and maintenance of natural killer cell lineages.

Flt3l related signaling pathway

JAK-STAT pathway: Binding of FLT3L to FLT3 induces phosphorylation and activation of Janus kinases (JAKs) which then activate STAT proteins.

Ras-Raf-MEK-ERK pathway: FLT3L stimulation leads to activation of the Ras GTPase and downstream Raf, MEK and ERK kinases.

PI3K-Akt pathway: FLT3L receptor ligation activates the phosphoinositide 3-kinase (PI3K) which triggers the Akt signaling cascade.

FLT3L Related Diseases

Acute myeloid leukemia (AML): FLT3 receptor mutations seen in around 30% of AML cases, linked to poorer prognosis.

Immunodeficiencies: Deficiencies in FLT3L or its receptor FLT3 can impair dendritic cell development and function.

Autoimmune diseases: FLT3 hyperactivity has been implicated in autoimmune conditions like rheumatoid arthritis.

Hematopoietic stem cell mobilization failure: Low FLT3L levels impede stem cell recruitment into peripheral blood circulation.

Biomedical Application of FLT3L Protein

•  Cancer immunotherapy: Used as an adjuvant to boost dendritic cell responses against tumors.
•  Bone marrow transplantation: Help promote stem cell engraftment after hematopoietic stem cell transplantation.
•  Wound healing: May accelerate healing through mobilization of progenitor cells to injury sites.
•  Dendritic cell vaccines: Added to cultures to generate ex vivo dendritic cells for anticancer/antiviral vaccines.

(Paul Milne, 2019)

Fig3. Serum Flt3L at day 26 in patients who subsequently achieved or did not achieve CR. Dotted line indicates optimal cut point identified by the ROC curve: 116 pg/mL (Mann-Whitney UP value).

Case 2: Clappaert EJ, Kancheva D, Brughmans J, et al. Flt3L therapy increases the abundance of Treg-promoting CCR7+ cDCs in preclinical cancer models. Front Immunol. 2023 Aug 9;14:1166180. doi: 10.3389/fimmu.2023.1166180. PMID: 37622122; PMCID: PMC10445485.
Flt3L is a cytokine required for DC development that can increase DC abundance in the tumor when administered therapeutically. However, the impact of Flt3L on the phenotype of distinct cDC subsets in the tumor microenvironment is still largely undetermined. Here, using multi-omic single-cell analysis, researchers show that Flt3L therapy increases all cDC subsets in orthotopic E0771 and TS/A breast cancer and LLC lung cancer models, but this did not result in a reduction of tumor growth in any of the models.

Fig4. Flt3L therapy does not improve the αCD40-mediated tumor-growth reduction. (D) E0771 tumor growth upon Flt3L+αCD40 therapy.

Flt3l has several biochemical functions, for example, cytokine activity,protein homodimerization activity,receptor tyrosine kinase binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Flt3l itself. We selected most functions Flt3l had, and list some proteins which have the same functions with Flt3l. You can find most of the proteins on our site.

Flt3l has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Flt3l here. Most of them are supplied by our site. Hope this information will be useful for your research of Flt3l.