PDGFRA - Platelet-derived growth factor receptor alpha - human protein (Function)
 
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PDGFRA »  Platelet-derived growth factor receptor alpha   [ EC 2.7.10.1 ]  (PDGFR-alpha)
 
Protein also known as:  Alpha-type platelet-derived growth factor receptor; CD antigen CD140a.
Gene name:  PDGFRA
Entry whose protein(s) existence is based on evidence at protein level
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1 385 3
GENE REF ISO

Function

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Overview 
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor.  
15
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Platelet-derived growth factor alpha-receptor activitydefinition[GO:0005018]  
4
  • BHF-UCL
  • UniProtKB
Platelet-derived growth factor bindingdefinition[GO:0048407]  
4
  • BHF-UCL
  • UniProtKB
Platelet-derived growth factor receptor bindingdefinition[GO:0005161]  
1
  • BHF-UCL
Protein bindingdefinition[GO:0005515]  
8
  • IntAct
  • UniProtKB
Protein homodimerization activitydefinition[GO:0042803]  
1
  • BHF-UCL
Transmembrane receptor protein tyrosine kinase activitydefinition[GO:0004714]  
1
  • UniProtKB
Vascular endothelial growth factor bindingdefinition[GO:0038085]  
1
  • BHF-UCL
Vascular endothelial growth factor-activated receptor activitydefinition[GO:0005021]  
1
  • BHF-UCL
GO biological process 
Adrenal gland developmentdefinition[GO:0030325] silver  
1
  • Ortholog Compara
Cardiac myofibril assemblydefinition[GO:0055003]  
1
  • Ortholog Curator
Cell activationdefinition[GO:0001775]  
1
  • BHF-UCL
Cell chemotaxisdefinition[GO:0060326]  
1
  • UniProtKB
Cellular response to amino acid stimulusdefinition[GO:0071230] silver  
1
  • Ortholog Compara
Embryonic cranial skeleton morphogenesisdefinition[GO:0048701]  
1
  • Ortholog Curator
Embryonic digestive tract morphogenesisdefinition[GO:0048557]  
1
  • Ortholog Curator
Embryonic skeletal system morphogenesisdefinition[GO:0048704]  
1
  • Ortholog Curator
Estrogen metabolic processdefinition[GO:0008210] silver  
1
  • Ortholog Compara
Extracellular matrix organizationdefinition[GO:0030198] silver  
1
  • Ortholog Compara
Face morphogenesisdefinition[GO:0060325] silver  
1
  • Ortholog Compara
Hematopoietic progenitor cell differentiationdefinition[GO:0002244] silver  
1
  • Ortholog Compara
In utero embryonic developmentdefinition[GO:0001701] silver  
1
  • Ortholog Compara
Leydig cell differentiationdefinition[GO:0033327] silver  
1
  • Ortholog Compara
Lung developmentdefinition[GO:0030324] silver  
1
  • Ortholog Compara
Luteinizationdefinition[GO:0001553]  
1
  • Ortholog Curator
Male genitalia developmentdefinition[GO:0030539] silver  
1
  • Ortholog Compara
Metanephric glomerular capillary formationdefinition[GO:0072277]  
1
  • Ortholog Curator
Negative regulation of platelet activationdefinition[GO:0010544]  
1
  • UniProtKB
Odontogenesis of dentin-containing toothdefinition[GO:0042475] silver  
1
  • Ortholog Compara
Palate developmentdefinition[GO:0060021] silver  
1
  • Ortholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
3
  • UniProtKB
  • BHF-UCL
Phosphatidylinositol-mediated signalingdefinition[GO:0048015]  
1
  • UniProtKB
Platelet aggregationdefinition[GO:0070527]  
1
  • UniProtKB
Platelet-derived growth factor receptor signaling pathwaydefinition[GO:0048008]  
2
  • BHF-UCL
Platelet-derived growth factor receptor-alpha signaling pathwaydefinition[GO:0035790]  
1
  • UniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
2
  • BHF-UCL
  • UniProtKB
Positive regulation of cell proliferationdefinition[GO:0008284]  
1
  • UniProtKB
Positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathwaydefinition[GO:0038091]  
1
  • BHF-UCL
Positive regulation of cytosolic calcium ion concentrationdefinition[GO:0007204]  
1
  • UniProtKB
Positive regulation of DNA replicationdefinition[GO:0045740]  
1
  • BHF-UCL
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • UniProtKB
Positive regulation of fibroblast proliferationdefinition[GO:0048146]  
1
  • BHF-UCL
Positive regulation of phosphatidylinositol 3-kinase activitydefinition[GO:0043552]  
1
  • UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
1
  • UniProtKB
Positive regulation of phospholipase C activitydefinition[GO:0010863]  
1
  • UniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
3
  • UniProtKB
  • BHF-UCL
Regulation of actin cytoskeleton reorganizationdefinition[GO:2000249]  
1
  • UniProtKB
Regulation of chemotaxisdefinition[GO:0050920]  
1
  • UniProtKB
Regulation of mesenchymal stem cell differentiationdefinition[GO:2000739]  
1
  • UniProtKB
Retina vasculature development in camera-type eyedefinition[GO:0061298]  
1
  • Ortholog Curator
Signal transduction involved in regulation of gene expressiondefinition[GO:0023019] silver  
1
  • Ortholog Compara
Viral processdefinition[GO:0016032]  
1
  • UniProtKB KW
Wound healingdefinition[GO:0042060]  
1
  • Ortholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
2
  • PROSITE-ProRule
  • UniProtKB
It is regulated in the following manner
Present in an inactive conformation in the absence of bound ligand. Binding of PDGFA and/or PDGFB leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib, nilotinib and sorafenib.  
4
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Calcium signaling pathway  hsa04020+5156  
Cytokine-cytokine receptor interaction  hsa04060+5156  
Endocytosis  hsa04144+5156  
Focal adhesion  hsa04510+5156  
Gap junction  hsa04540+5156  
Glioma  hsa05214+5156  
HTLV-I infection  hsa05166+5156  
MAPK signaling pathway  hsa04010+5156  
Melanoma  hsa05218+5156  
Pathways in cancer  hsa05200+5156  
Prostate cancer  hsa05215+5156  
Regulation of actin cytoskeleton  hsa04810+5156  
According to Reactome, this protein belongs to the following pathways:
Constitutive PI3K/AKT Signaling in Cancer  REACT_147727  
Downstream signal transduction  REACT_17025  
PIP3 activates AKT signaling  REACT_75829  
Signaling by PDGF  REACT_16888  
 

Keywords

Biological process 
Chemotaxis  definition   [KW-0145]
Host-virus interaction  definition   [KW-0945]
Molecular function 
Developmental protein  definition   [KW-0217]
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PDGFRA
GenomeRNAi: 5156
PRO: PR:P16234
Chemistry
GuidetoPHARMACOLOGY: 1803