FLT3 Signaling
Flt-3/Flk-2 ligand (FL, Flt3-L, fms-like tyrosine-kinase 3 ligand) is a transmembrane 30 kDa glycoprotein that activates the Flt3 (CD135, FLK2) receptor. The Flt-3 receptor is a member of the class III subfamily of receptor tyrosine kinases (RTK) that includes the PDGF receptor; CSFIR (colony stimulating factor 1 receptor) (FMS) and KIT (stem cell factor receptor, steel locus factor receptor, SLFR). Flt-3 is expressed primarily in hematopoietic stem cells (myelomonocytic, monocytic, pre-G and pro-B lineages) and acute leukemia T, B and myeloid blast cells. Tissues that contain Flt-3 expressing cells include bone marrow, thymus, spleen, liver, testis, placenta, CNS and lymph nodes.
FL (Flt3-L), which is structurally related to M-CSF (CSF-1) and SCF (KL), is expressed in a broad range of cell types. FL is biologically active on the cell surface or in a cleaved soluble form. The binding of FL to the Flt-3 receptor typically produces modest growth and differentiation effects. However, in the presence of a variety of cytokines FL binding to Flt-3 promotes strong growth and differentiation effects. Fl synergizes with GM-CSF, IL-1, IL-3, IL-6, SCF (KL), M-CSF, G-CSF, IL-7 and TPO.
Flt-3 ligand, in synergy with other cytokines, stimulates the growth and differentiation of a number of important cell populations. Activation of Flt-3 stimulates the growth and differentiation of very early stem cells involved in hematopoiesis, myelopoiesis, erythropoiesis and megakaryopoiesis. Flt-3 activation mobilizes hematopoietic progenitor cells into peripheral blood and induces proliferation of myeloid and dendritic cells (DC). Dysregulation of Flt-3 has been associated with acute leukemia(s) involving myeloid (AML), T, and B blast cell(s).
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