CD310 FLT4 (fms-related tyrosine kinase 4), VEGFR3 (vascular endothelial growth factor receptor-3)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Placenta
Kidney
Heart
Lung
Epithelium
Sarcoma Cell
146 / 146

Expression

CD310 is expressed in placenta, lung, heart and kidney, but does not seem to be expressed in pancreas and brain.  Expression is on lymphatic endothelium of normal and malignant tissues and on spindle cells of Kaposi's sarcoma.



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

CD310 is a single-pass type-1 1274 aa glycoprotein.  It contains a 24 aa signal sequence, a 751 aa extracellular domain which contains 7 Ig-like C2-type domains and 12 N-linked glycosylation sites, a transmembrane domain and a 501 aa intracellular cytoplasmic domain which contains a 329 aa protein kinase domain.  CD310 together with CD308 and CD309 constitute the flt subfamily of receptors.  CD310 is part of the type-3 tyrosine kinase receptors.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD310 has 12 N-linked glycoslation sites.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD310

CD310 binds vascular endothelial growth factor (VEGF).


Function
CD310 has a tyrosine kinase activity.  Ligand activated CD310 recruits CD192 (CKR2) and induces a signal cascade, resulting in the activation of c-Jun N-terminal kinase-1/2 (JNK1/2) and signaling for cell survival.  Phosphorylation of tyrosines Y1230 and Y1231 leads to the recruitment of Grb2 which induces activation of AKT and ERK1/2 signaling and ultimately c-JUN expression and pro-survival signaling.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD310 IN INTACT ANIMAL

CD310 is a specific marker of lympathic endothelium and with VEGFD in gastric adencarcinoma patients correlates with a poor prognosis.  Soluble CD310 decoy receptors are potential therapeutic agents for the prevention of metastasis via the lymphatic system for some tumors such as melamona and prostate cancer.  CD310 is critical for angiogenesis in embryos and plays a role in angiogenesis and lymphangiogenesis in adults.  Defects in CD310 are the cause of congenital heritary lymphedema known as Milroy disease which results in swelling of extremities due to altered lymphatic flow and also juvenile hemangioma causing tumors in infancy.  Miroy disease is caused by autosomal dominant mutations and the onset of the lymphoedema can begin at birth and is severe enough to physically impair patients.  Juvenile hemangiomas are related to CD310 mutations and are characterized by benign vascular lesions that expand in earlyu childhood but spontaneously involute over several years.

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD310: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD310: No information.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 2324P35916
Antibodies

Revised June 25, 2008


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