Recombinant Human FIt-3 Ligand/FLT3L

Flt-3 Ligand (FLT3L) is an alpha-helical cytokine that promotes the differentiation of multiple hematopoietic cell lineages ^[1-3]. Mature human Flt-3 Ligand consists of a 158 amino acid (aa) extracellular domain (ECD) with a cytokine-like domain and a juxtamembrane tether region, a 21 aa transmembrane segment, and a 30 aa cytoplasmic tail ^[4-7]. Within the ECD, human Flt-3 Ligand shares 71% and 65% aa sequence identity with mouse and rat Flt-3 Ligand, respectively ^[4-6]. The human and mouse Flt-3 Ligand proteins show cross-species activity. Flt-3 Ligand is also structurally related to M-CSF and SCF. Flt-3 Ligand is widely expressed in various human and mouse tissues. It is expressed as a noncovalently-linked dimer by T cells and bone marrow and thymic fibroblasts ^{[1, 8]}. Each 36 kDa chain of the Flt-3 Ligand dimer carries approximately 12 kDa of N- and O-linked carbohydrates ^[8]. Alternate splicing and proteolytic cleavage of the transmembrane form of the Flt-3 Ligand protein can generate a soluble 30 kDa fragment that includes the cytokine-like domain ^{[4, 8]}. Alternate splicing of human Flt-3 Ligand also generates membrane-associated isoforms that contain either a truncated cytoplasmic tail or an 85 aa substitution following the cytokine-like domain in the ECD of the Flt-3 Ligand protein ^{[4, 5, 8]}. Both transmembrane and soluble forms of Flt-3 Ligand signal through the tyrosine kinase receptor Flt-3/Flk-2 ^{[3, 4, 6, 7]}. Flt-3 Ligand induces the expansion of monocytes and immature dendritic cells as well as early B cell lineage differentiation ^{[2, 9]}. Additionally, Flt-3 Ligand synergizes with IL-3, GM-CSF, and SCF to promote the mobilization and myeloid differentiation of hematopoietic stem cells ^[4-6]. Flt-3 Ligand also cooperates with IL-2, IL-6, IL-7, and IL-15 to induce NK cell development and with IL-3, IL-7, and IL-11 to induce terminal B cell maturation ^{[1, 10]}.

Reference

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[2]. Dong, J. et al. (2002) Cancer Biol. Ther. 1:486.

[3]. Gilliland, D.G. and J.D. Griffin (2002) Blood 100:1532.

[4]. Hannum, C. et al. (1994) Nature 368:643.

[5]. Lyman, S.D. et al. (1994) Blood 83:2795.

[6]. Lyman, S.D. et al. (1993) Cell 75:1157.

[7]. Savvides, S.N. et al. (2000) Nat. Struct. Biol. 7:486.

[8]. McClanahan, T. et al. (1996) Blood 88:3371.

[9]. Diener, K.R. et al. (2008) Exp. Hematol. 36:51.

[10]. Farag, S.S. and M.A. Caligiuri (2006) Blood Rev. 20:123.