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Protein: FLT3_MOUSE

Receptor-type tyrosine-protein kinase FLT3

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. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. more...

ENZYME REGULATION: Present in an inactive conformation in the absence of bound ligand. FLT3LG-binding leads to dimerization and activation by autophosphorylation.

SUBUNIT: Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. One homodimer interacts with one FLT3LG molecule. Interacts with FIZ1 following ligand activation. Interacts with FES, FER and GRB2. Interacts with PTPRJ/DEP-1 and PTPN11/SHP2 (By similarity).

SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. Endoplasmic reticulum lumen (By similarity). 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 (By similarity).

TISSUE SPECIFICITY: Hematopoietic stem and progenitor cell- enriched populations. Found in brain, placenta and testis.

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 (By similarity).

PTM: N-glycosylated, contains complex N-glycans with sialic acid (By similarity).

PTM: Autophosphorylated 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 (By similarity).

PTM: Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein ligase SIAH1 after autophosphorylation, leading to its proteasomal degradation (By similarity). DISRUPTION PHENOTYPE: No visible phenotype. Mice are born at the expected Mendelian rate, develop normally and are fertile. They show normal blood cell counts, excepting reduced levels of primitive B-cell progenitors. Mice lacking both Flt3 and Kit show a reduction in both lymphoid and myeloid cell lineages. They appear normal, but are born at a lower frequency than expected and exhibit severely reduced viability after 3 weeks, none surviving more than six weeks.

SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.

SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

SIMILARITY: Contains 1 protein kinase domain.

GENE SYNONYMS: Flk-2 Flt-3.

COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.

No pathway or interaction information available for this record.

 

Organism:

  • Mus musculus

Gene Symbol:

  • Flt3

Synonyms:

  • FL cytokine receptor
  • Fetal liver kinase 2
  • Tyrosine-protein kinase receptor flk-2
  • FLT-3
  • FLK-2
  • CD135
  • Fms-like tyrosine kinase 3
  • 2.7.10.1

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