FLT3 (fms-related tyrosine kinase 3) is a tyrosine kinase receptor and the gene is localized to human chromosome 13q12. The encoded protein is composed of 993 amino acids, and consists of five immunoglobulin (Ig)-like domains in its exoplasmic region. It is also composed of a transmembrane region, a juxtamembrane domain, and two tyrosine kinase domains in its intracellular domain. The tyrosine kinase domains are linked via a kinase-insert domain.
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FLT3 (fms-related tyrosine kinase 3), upon interaction with its ligand, undergoes conformational changes to form homodimers. This results in phosphorylation and activation of downstream signaling pathways including phosphatidylinositol 3-kinase (PI3K/AKT), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and signal transducer and activator of transcription 5 (STAT5) pathways. Internal tandem duplication (ITD) mutation or a point mutation in juxtamembrane domain-coding region or within the activation loop domain, respectively, of this gene lead to its constitutive action. FLT3/ITD mutation is associated with later stages of acute myeloid leukemia (AML) pathogenesis. These patients have poor prognosis.
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