CD140a PDGFRα (platelet-derived growth factor receptor α polypeptide)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Endothelial Cell
Fibroblast
Erythroid Cell
Mesenchymal Cell
Bone Marrow
Myeloid Cell
Glial Cells
Monocyte
Osteoblast
180 / 180

Expression
CD140α is expressed on mesenchymal cell, erythroid and myeloid precursors in bone marrow, monocytes, fibroblasts, endothelial cells, osteoblasts and glial cells.

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

CD140α is a single-pass type-1 glycoprotein.  It contains a 501 aa extracellular domain which contains 3 Ig-like C2-type domains and 8 potential N-linked glycosylation sites, a 25 aa transmembrane domain and a 540 aa cytoplasmic domain which contains a protein kinase domain which split in two by an insert domain, a membrane-proximal serine-rich region and two ATP-binding sites.  CD140α binding induces either homodimerization or heterodimerization with the CD140β activation and autophosphorylation.

MOLECULAR MASS
Cell Type Unreduced Reduced
180 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD140α

CD140α binds platelet-growth factor.

Function
CD140α is a receptor for platelet-derived growth factor.  CD140α encodes a cell surface tyrosine receptor for members of the platelet-derived growth factor family.  These growth factors are mitogens for cell of mesenchymal origin.  The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer composed of both platelet-derived growth receptor α and β polypeptides.  Activation and autophorsphorylation of CD140α leads to the recruitment of SH-2 domain containing signal transduction proteins and activation of signaling enzymes including Src, PI3K and phospholipase Cγ1 (PLCγ) resulting in a complex series of signaling events that have not been fully characterized.  The predominant role of CD140α is to promote the proliferation of precursor populations of various cell types including lung alveolar smooth muscle cells, oligodendrocytes, intestinal villae and dermal papillae.  Studies in knockout mice, where homozygosity is lethal, indicate that the α form of the CD140α is particularly important for kidney development since mice heterozygous for the receptor exhibit defective kidney phenotypes.

BIOCHEMICAL ACTIVITY

The major biochemical difference between CD140α and CD140β is the preferential binding of RasGAP to CD140β but not to CD140α and Crk association with CD140α but not CD140β.  Both RasGAP ande Crk have negatively regulatory effects.

DISEASE RELEVANCE AND FUNCTION OF CD140α IN INTACT ANIMAL

Defects in CD140α are the cause of some cases of hypereosinophilic sydrome (HES) which is a rare hematologic disorder characterized by sustained overproduction of eosinophils in the bone marrow, eosinophilia, tissue infiltration and organ damage.  Deletion of CD140α results in embryonic lethality.  CD140α is a promising therapeutic target in the treatment of several tumors, particularily those tumors where autocrine CD140α stimulation is important.  Several CD140α antagonists are currently being investigated. 

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD140α: No information.

SUBSTRATES: No information

ENZYMES WHICH MODIFY CD140α: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 5156P16234
Antibodies

Revised June 25, 2008


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