CD202b 

TEK tyrosine kinase endothelial (venous malformations, multiple cutaneous and mucosal), TIE2

Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Endothelial Cell
Stem Cell
Placenta
Lung
Hematopoietic Cell
145 / 145

Expression
CD202b, the TEK receptor tyrosine, is expressed on a subset of CD34+ hematopoietic stem cells, early hematopoietic cells, and almost exclusively on vascular endothelial cells and their progenitors and aggioblasts.  The expression is seen in mice, rats and humans.  CD202b is functionally important in mouse and human in the remodeling and repair of blood vessels.  Expression has been directly found in placenta and lung with a lower level in the umbilical vein, brain and kidney.


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

CD202b is a single-pass type-1 glycoprotein.  It contains an extracellular domain which contains a C-terminal Ig-like C2-type loop, 3 epidermal growth factor-like domains followed by another Ig-like C2-type domain, 3 fibronectin type-3-like repeats and 9 potential N-linked glycosylation sites, a 25 aa transmembrane domain and a intracellular cytoplasmic domain which contains a split catalytic tyrosine kinase domain.

MOLECULAR MASS
Cell Type Unreduced Reduced
Endothelial cell 145 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
CD202b binds angiopoietins Ang-1, Ang-2 and Ang-4.

LIGANDS AND MOLECULES ASSOCIATED WITH CD202b
Molecule Comment
Angiopoietin-1 Ligands for TEK receptor
Angiopoietin-2 Acts as a natural antagonists for Angiopoietin-1


Function
CD202b is an endothelial-specific membrane receptor tyrosine kinase that plays a crucial role in the secondary stages of blood vessel formation during which vessels remodel, mature and form complex hierarchial networks.  It is not required for endothelial cell proliferation during vasculogenesis, but plays a critical role in the integrity of vessels during maturation and maintenance/remodeling.  CD202b is the receptor for and binds with angiopoietin 1 resulting in activation and phosphorylation and the activation of the Akt signaling pathway.  This pathway is associated with increased survival of endothelial cells under stress conditions. 
Angiopoietin 2 is a naturally occurring molecule which blocks binding of angiopoietin 1 to CD202b.  It appears to be involved in postnatal angiogenesis and vascular and lymphatic remodeling.  In some in vitro studies, Ang-2 was found to antagonize the effects of the Ang-1/CD202b interaction.  CD202b is required for the development and proliferation of hematopoietic stem cells as well as the formation of vascular networks.  The interaction of Ang-1 expressing subendosteal osteoclasts with CD202b+ hematopoietic stem cells (HSC) has been shown to maintain the HSC in anti-apoptotic and quiescent stae ensuring their long ability to repopulate the bone marrow.
 
BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD2020b IN INTACT ANIMAL

CD202-deficient mice die during embryogenesis at approximately embryonic day 10.5 because of vascular defects particularly vascularization and trabeculation of the heart.  Aortas of CD200 null mice have fewer endothelial cells and significantly reduced numbers of smooth muscle cells.  These cells also fail to attach to the blood vessel.  Mutations in CD202b are associated with inherited venous malformations, both multiple cutaneous and mucosal.  The defect is associated with point mutations in the tyrosine kinase domain of CD202b resulting in a active CD202b.  These patients, typically have large, thin-walled veins with fewer pericytes and smooth muscle cells than the equivalent normal veins.  The signaling pathway appears to be critical for endothelial cell-smooth muscle cell communication in venous morphogenesis.  CD202b is a useful marker of neo-angiogenesis in tumors and a prognostic indicator of metastasis in breast carcinoma and astrocytomas.  Increased CD202b expression correlates with increased tumor size of differentiation of hepatocarcinomas.


Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD202b: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD202b: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 7010Q02763
Antibodies

Revised June 25, 2008


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