CD135 FLT3 (fms-like tyrosine kinase 3), flk-2, STK1
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 1 glycoprotein
Spleen
Stem Cell
Lung
Bone Marrow
Brain
B Cell
Myelomonocytic cell
Nervous system
130 / 130
155 / 155

Expression
CD135 is expressed on multipotential, myelomonocytic and primitive B cell progenitors.  The murine orthlogue is detected in the nervous system, gonads and brain.  It is expressed on CD34+ hematopoietic stem cells.   mRNA for human and mouse CD135 ligand is widespread in adult and fetal tissue with the highest expression in the spleen, lung and bone marrow cells.  Human CD135 mRNA is high in peripheral blood mononuclear cells.  Surface expression has been demonstrated on cell lines by binding recombinant CD135.  A mouse thymic stromal line secretes a soluble form of CD135 ligand.


Structure
MOLECULAR FAMILY NAME: Belongs to the tyrosine kinase receptor family.

CD135 is a single-chain type-1 993 aa glycoprotein.  It contains a 541 aa extracellular 
domain which contains 5 Ig-like C2 type domains, a 21 aa transmembrane domain and a 431 aa cytoplasmic region which contains a hydrophilic protein kinase insertion that divides the intracellular catalytic region in 2 domains.  CD135 is a member of the type-3 receptor tyrosine kinase family which includes c-kit, macrophage colony-stimulating factor CD115 (M-CSFR) and platelet derived growth factor receptor CD140 (PDGFR).  A short sequence that shows no similarity to other proteins precedes the 1st IgSF domain.  The IgSF domains contain a number of cysteines in atypical positions and so the domain assignments are tentative.  Domains 1 and 2 show substantial similarity to domains 4 and 5, suggesting an internal duplication event during evolution.  Cell lines expressing CD135 show protein products of 130 kDa and 160 kDa, probably due to differential glycosylation.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Ba/F3 cells transfected with the human FLT3 cDNA 130 kDa 155 kDa
Leukemic cells 130 kDa 155/160 kDa

MOLECULAR MASS OF FLT3L
Cell Type Unreduced Reduced
Soluble 30 kDa

POST-TRANSCRIPTIONAL MODIFICATION

CD135 is not described in human but the receptor splicing is seen in the mouse.

POST-TRANSLATIONAL MODIFICATION

CD135 has 10 potential asparagine-linked glycosylation sites in the extracellular region.  The degree of glycosylation varies between cell lines and tyrosine phosphorylation.

Ligands
CD135 binds to the FLT3L which binds to the FLT3 (flk-2) receptor.

LIGANDS AND MOLECULES ASSOCIATED WITH CD135
Molecule Comment
FL (FLT3 ligand) Type-1 transmembrane protein with an N-terminal signal peptide of 26 aa, followed by a 156 aa extracellular region, a 23 aa transmembrane domain, and a short 30 aa cytoplasmic region. Alternative mRNA splicing produces membrane-bound and soluble isoforms (both active). Synergizes with other cytokines for proliferation and differentiation of hematopoietic progenitor cells



Function
CD135 is a tyrosine kinase receptor.  The growth factor receptor functions for early hematopoietic stem and progenitors cells.  CD135 is likely to be involved in growth and differentiation of primitive hematopoietic cells.  Anti-sense RNA of CD135 has been shown to inhibit colony-forming activity of long-term bone marrow culture cells. 

BIOCHEMICAL ACTIVITY

CD135 acts as a growth factor receptor and the tyrosine kinase receptor.

DISEASE RELEVANCE AND FUNCTION OF CD135 IN INTACT ANIMAL

CD135 is expressed in the majority of AML, ALL and CML-BC.  Targeted CD135 disruption in knockout mice impaired the developmental capacity of primitive progenitor cells of all hematopoietic lineages with the greatest impact on lymphopoietic precursors.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD135: No information.

SUBSTRATES
Molecule Comment
GAP Associates with CD135, activated by phosphorylation
PLCg Associates with CD135, activated by phosphorylation
VAV Seems not to associate with CD135 but is phosphorylated after CD135 activation
SHC Seems not to associate with CD135 but is phosphorylated after CD135 activation
PI3 kinase Associates through SH2 domains to Tyr-phosphorylated site on the carboxy tail of CD135
GRB2 Associates through SH2 domains to Tyr-phosphorylated site on the carboxy tail of CD135

ENZYMES WHICH MODIFY CD135

Phosphates have not yet been described.

ADDITIONAL INSIGHTS

The most primitive hematopoietic progenitor cells are expressed at low levels of CD135.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 2322P36888
MouseA39931Q00342M64689
MouseX59398
MouseP49772U04807
Antibodies

Revised June 25, 2008


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