CD309 KDR (kinase insert domain receptor, a type III receptor tyrosine kinase), VEGFR-2, FLK1
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Endothelial Cell
Stem Cell
Tumor Cell
Megakaryocyte
Platelet
Progenitor Cell
Muscle, Smooth
Pancreas
Retina
230 / 230

Expression
CD309 is expressed on vascular endothelial cells, megakaryocytes, platelets, retinal progenitors, smooth muscle, pancreatic duct cells, some tumor cells, precursor cells and primtive stem cell subsets.  Expression is in most embryonic tissues but is lower before birth and is expressed at low levels in quiescent adult endothelium.  Increased expression is associated with pathological angiogenesis associated with tumors and diabetic retinopathy.  Expression has been reported on hematopoietic presursors but this has not been confirmed.

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

CD309 is a single-pass type-1 glycoprotein.  It contains an extracellular domain which contains 7 Ig-like C2-type domains, a transmembrane domain and an intracellular cytoplasmic domain with a kinase insert sequence.  The first 3 extracellular domains are required for ligand binding whereas the last 4 are involved in receptor dimerisation.  There was an ATP binding site, a membrane spanning region, a split tyrosine kinase regions, a platelet-derived growth factor receptor, a colony stimulating factor-1 receptor, a fibroblast growth factor receptor, and KIT.  CD309 together with CD308 and CD310 constitute the flt subfamily of resceptor.  The type-3 receptor tyrosine kinase binds CD309 with high affinity. 

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION: No information.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD309

CD309 associates with vascular endothelial growth factors (VEGF).

Function
CD309 is expressed early in development by endothelial cell precursors and is thought to be important in angiogenesis and related functions.  Ligand binding leads to receptor dimerization and autophosphorylation and migration, inducing vascular permeability and release of niteous oxide.  The receptor engagement stimulates expression of proteases required for angiogenesis.  CD309 has also been identified as a positive functional marker defining stem cells distinguishing them from progenitors.  CD309 binds adhesion and cell signaling and is a receptor of VEGF or VEGFC and has a tyroine-protein kinase activity.  The VEGF-kinase ligand/receptor signaling system plays a role in vascular development and regulation of vascular permeability.  CD309 interacts with SHB upon VEGF activation. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD309 IN INTACT ANIMAL

Because of its role in angiogenesis in tumors and diabetic retinopathy, the CD309 signaling pathway is a major therapeutic target.  Kinease inhibitors and antibodies designed to inhibit ligand binding are undergoing clinical trials.  Knockout mice die between embryonic days 8.5 and 9.5 as a result of defects in hematopoiesis and endothelial cell development.


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD309: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD309: No information.

ADDITIONAL INSIGHTS

For further information see Ziegler, B. L. et al (1999) Science 285: 1553-1558.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3791P35968
Antibodies

Revised June 25, 2008


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