Flt-3 Ligand active protein
Human Flt-3 Ligand
NCBI and Uniprot Product Information
NCBI Description
This gene 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. [provided by RefSeq, Jul 2008]
Uniprot Description
Function: Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. Ref.1 Ref.10 Ref.11 Ref.12 Ref.14 Ref.17 Ref.20 Ref.22 Ref.23 Ref.24 Ref.31
Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.13
Enzyme regulation: Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to dimerization and activation by autophosphorylation. Ref.24 Ref.27
Subunit structure: Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. Interacts with FIZ1 following ligand activation
By similarity. Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. Interacts with PTPRJ/DEP-1 and PTPN11/SHP2. Ref.9 Ref.10 Ref.15 Ref.20 Ref.23 Ref.28
Subcellular location: Membrane; Single-pass type I membrane protein. Endoplasmic reticulum lumen. Note: Constitutively activated mutant forms with internal tandem duplications are less efficiently transported to the cell surface and a significant proportion is retained in an immature form in the endoplasmic reticulum lumen. The activated kinase is rapidly targeted for degradation. Ref.7 Ref.13 Ref.17
Tissue specificity: Detected in bone marrow, in hematopoietic stem cells, in myeloid progenitor cells and in granulocyte/macrophage progenitor cells (at protein level). Detected in bone marrow, liver, thymus, spleen and lymph node, and at low levels in kidney and pancreas. Highly expressed in T-cell leukemia. Ref.1 Ref.2 Ref.7 Ref.17
Domain: The juxtamembrane autoregulatory region is important for normal regulation of the kinase activity and for maintaining the kinase in an inactive state in the absence of bound ligand. Upon tyrosine phosphorylation, it mediates interaction with the SH2 domains of numerous signaling partners. In-frame internal tandem duplications (ITDs) result in constitutive activation of the kinase. The activity of the mutant kinase can be stimulated further by FLT3LG binding. Ref.16
Post-translational modification: N-glycosylated, contains complex N-glycans with sialic acid. Ref.13 Ref.23 Ref.28Autophosphorylated on several tyrosine residues in response to FLT3LG binding. FLT3LG binding also increases phosphorylation of mutant kinases that are constitutively activated. Dephosphorylated by PTPRJ/DEP-1, PTPN1, PTPN6/SHP-1, and to a lesser degree by PTPN12. Dephosphorylation is important for export from the endoplasmic reticulum and location at the cell membrane. Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.18 Ref.23 Ref.30 Ref.31Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein ligase SIAH1 after autophosphorylation, leading to its proteasomal degradation.
Involvement in disease: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.Note: The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase. Ref.8 Ref.9 Ref.11 Ref.12 Ref.16 Ref.29 Ref.30 Ref.31
Miscellaneous: Can be used as diagnostic tool to establish the exact cause of acute myeloid leukemia, and to determine the optimal therapy.
Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.Contains 1 Ig-like C2-type (immunoglobulin-like) domain.Contains 1 protein kinase domain.
Research Articles on Flt-3 Ligand
Similar Products
Product Notes
The Flt-3 Ligand flt3 (Catalog #AAA692173) is an Active Protein produced from E Coli and is intended for research purposes only. The product is available for immediate purchase. The Human Flt-3 Ligand reacts with Human and may cross-react with other species as described in the data sheet. The amino acid sequence is listed below: TQDCSFQHSP ISSDFAVKIR ELSDYLLQDY PVTVASNLQD EELCGG LWRL VLAQRWMERL KTVAGSKMQG LLERVNTEIH FVTKCAFQPP P SCLRFVQTN ISRLLQETSE QLVALKPWIT RQNFSRCLEL QCQPDSS TLP PPWSPRPLEA TAPTA. It is sometimes possible for the material contained within the vial of "Flt-3 Ligand, Active Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
All products in the AAA Biotech catalog are strictly for research-use only, and are absolutely not suitable for use in any sort of medical, therapeutic, prophylactic, in-vivo, or diagnostic capacity. By purchasing a product from AAA Biotech, you are explicitly certifying that said products will be properly tested and used in line with industry standard. AAA Biotech and its authorized distribution partners reserve the right to refuse to fulfill any order if we have any indication that a purchaser may be intending to use a product outside of our accepted criteria.Disclaimer
Though we do strive to guarantee the information represented in this datasheet, AAA Biotech cannot be held responsible for any oversights or imprecisions. AAA Biotech reserves the right to adjust any aspect of this datasheet at any time and without notice. It is the responsibility of the customer to inform AAA Biotech of any product performance issues observed or experienced within 30 days of receipt of said product. To see additional details on this or any of our other policies, please see our Terms & Conditions page.Item has been added to Shopping Cart
If you are ready to order, navigate to Shopping Cart and get ready to checkout.
