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FLT3 encodes a class III receptor tyrosine kinase that regulates hematopoiesis. The receptor consists of an extracellular domain composed of five immunoglobulin-like domains, one transmembrane region, and a cytoplasmic kinase domain split into two parts by a kinase-insert domain. The receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia.Small D., Proc. Natl. Acad. Sci. U.S.A. 91:459-463(1994).Rosnet O., Blood 82:1110-1119(1993).Rosnet O., Genomics 9:380-385(1991).
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