Platelet-derived growth factor receptor alpha
Also known as: PDGFR2, PDGFRA, RHEPDGFRA
Function
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.
Classification
- Family (Pfam)
- PF07679 I-set, PF25305 Ig_PDGFR_d4, PF07714 PK_Tyr_Ser-Thr, PF22854 VEGFR1-3_N_Ig-like
- InterPro
- Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_I-set, Ig_sub, Ig_sub2, Kinase-like_dom_sf, PDGFRA, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS, VEGFR1-3_N_Ig-like
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 15
- 1GQ5 X-ray 2.20A
- 5GRN X-ray 1.77A
- 5K5X X-ray 2.17A
- 6A32 X-ray 1.87A
- 6JOI X-ray 3.10A
- 6JOJ X-ray 2.60A
- 6JOK X-ray 3.80A
- 6JOL X-ray 1.90A
- 7LBF EM 2.80A
- 7RAM EM 3.43A
- 8PQH X-ray 2.50A
- 8PQI X-ray 2.60A
- … and 3 more
A predicted model is available from AlphaFold.
Gene Ontology · 52
- GO:0005929 cilium
- GO:0005737 cytoplasm
- GO:0005789 endoplasmic reticulum membrane
- GO:0009897 external side of plasma membrane
- GO:0005794 Golgi apparatus
- GO:0016020 membrane
- GO:0005902 microvillus
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0032991 protein-containing complex
- GO:0043235 receptor complex
- GO:0005524 ATP binding
- GO:0160185 phospholipase C activator activity
- GO:0005018 platelet-derived growth factor alpha-receptor activity
- GO:0048407 platelet-derived growth factor binding
- GO:0005161 platelet-derived growth factor receptor binding
- GO:0042803 protein homodimerization activity
- GO:0004672 protein kinase activity
- GO:0044877 protein-containing complex binding
- GO:0004714 transmembrane receptor protein tyrosine kinase activity
- GO:0038085 vascular endothelial growth factor binding
- GO:0005021 vascular endothelial growth factor receptor activity
- GO:0055003 cardiac myofibril assembly
- GO:0001775 cell activation
- GO:0060326 cell chemotaxis
- GO:0016477 cell migration
- GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
- GO:0034614 cellular response to reactive oxygen species
- GO:0048701 embryonic cranial skeleton morphogenesis
- GO:0048557 embryonic digestive tract morphogenesis
- GO:0048704 embryonic skeletal system morphogenesis
- GO:0001553 luteinization
- GO:0072277 metanephric glomerular capillary formation
- GO:0010544 negative regulation of platelet activation
- GO:0038083 peptidyl-tyrosine autophosphorylation
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0070527 platelet aggregation
- GO:0048008 platelet-derived growth factor receptor signaling pathway
- GO:0035790 platelet-derived growth factor receptor-alpha signaling pathway
- GO:0050850 positive regulation of calcium-mediated signaling
- GO:0030335 positive regulation of cell migration
- GO:0008284 positive regulation of cell population proliferation
- GO:0038091 positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway
- GO:0050921 positive regulation of chemotaxis
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:0048146 positive regulation of fibroblast proliferation
- GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0046777 protein autophosphorylation
- GO:0032956 regulation of actin cytoskeleton organization
- GO:2000739 regulation of mesenchymal stem cell differentiation
- GO:0061298 retina vasculature development in camera-type eye
- GO:0042060 wound healing
Disease associations
- polyps, multiple and recurrent inflammatory fibroid, gastrointestinal MONDO:0008285
- gastrointestinal stromal tumor MONDO:0011719
- idiopathic hypereosinophilic syndrome MONDO:0011895
Drugs targeting this protein · 26
- VATALANIB inhibitor
- PAZOPANIB HYDROCHLORIDE inhibitor
- FORETINIB inhibitor
- FAMITINIB inhibitor
- SUNITINIB MALATE inhibitor
- SU-014813 inhibitor
- MASITINIB inhibitor
- REGORAFENIB inhibitor
- ILORASERTIB inhibitor
- AMUVATINIB inhibitor
- CRENOLANIB inhibitor
- TAK-593 inhibitor
- LINIFANIB inhibitor
- ORANTINIB inhibitor
- NINTEDANIB ESYLATE inhibitor
- AVAPRITINIB inhibitor
- RIPRETINIB inhibitor
- SERALUTINIB inhibitor
- CEDIRANIB inhibitor
- DOVITINIB inhibitor
- ENMD-981693 inhibitor
- XL-999 inhibitor
- SUNITINIB inhibitor
- MOTESANIB inhibitor
- QUIZARTINIB inhibitor
- MIDOSTAURIN inhibitor
Related proteins · sequence + function similarity
- Platelet-derived growth factor receptor alpha 0.99
- Platelet-derived growth factor receptor alpha 0.99
- Platelet-derived growth factor receptor alpha 0.98
- Platelet-derived growth factor receptor alpha 0.98
- Platelet-derived growth factor receptor alpha 0.94
- Platelet-derived growth factor receptor alpha 0.94
- Mast/stem cell growth factor receptor Kit 0.94
- Mast/stem cell growth factor receptor Kit 0.93
- Mast/stem cell growth factor receptor Kit 0.93
- Mast/stem cell growth factor receptor Kit 0.93
- Mast/stem cell growth factor receptor Kit 0.93
- Mast/stem cell growth factor receptor Kit 0.93
Co-cited proteins · studied together in the literature
- Platelet-derived growth factor receptor beta 10 shared papers
- SH2 domain-containing adapter protein F 1 shared papers
- Pre-mRNA 3'-end-processing factor FIP1 2 shared papers
- 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 1 shared papers
- Envelope glycoprotein O 1 shared papers
- Envelope glycoprotein L 2 shared papers
- Envelope glycoprotein B 1 shared papers
- Adapter molecule crk 1 shared papers
- Envelope glycoprotein H 2 shared papers
- Proto-oncogene tyrosine-protein kinase Src 1 shared papers
- 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 2 shared papers
- Phosphatidylinositol 3-kinase regulatory subunit alpha 2 shared papers
Literature · 45 cited papers
- Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry. Cell · 2021
- Human cytomegalovirus glycoprotein complex gH/gL/gO uses PDGFR-alpha as a key for entry. PLoS Pathog. · 2017
- PDGFRA-mutant syndrome. Mod. Pathol. · 2015
- The Casitas B lineage lymphoma (Cbl) mutant G306E enhances osteogenic differentiation in human mesenchymal stromal cells in part by decreased Cbl-mediated platelet-derived growth factor receptor alpha and fibroblast growth factor receptor 2 ubiquitination. J. Biol. Chem. · 2011
- Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease. Blood · 2011
- The low frequency of clinical resistance to PDGFR inhibitors in myeloid neoplasms with abnormalities of PDGFRA might be related to the limited repertoire of possible PDGFRA kinase domain mutations in vitro. Oncogene · 2011
- The glycoprotein B disintegrin-like domain binds beta 1 integrin to mediate cytomegalovirus entry. J. Virol. · 2010
- Role of platelet-derived growth factors in physiology and medicine. Genes Dev. · 2008
- Platelet-derived growth factor receptor-alpha: a novel therapeutic target in human hepatocellular cancer. Mol. Cancer Ther. · 2007
- PDGF receptors as targets in tumor treatment. Adv. Cancer Res. · 2007
- Patterns of somatic mutation in human cancer genomes. Nature · 2007
- PI3-kinase/Akt-dependent antiapoptotic signaling by the PDGF alpha receptor is negatively regulated by Src family kinases. FEBS Lett. · 2006
- … and 33 more in the literature graph