Platelet-derived growth factor receptor beta

Details

Name
Platelet-derived growth factor receptor beta
Synonyms
  • 2.7.10.1
  • Beta platelet-derived growth factor receptor
  • Beta-type platelet-derived growth factor receptor
  • CD140 antigen-like family member B
  • PDGF-R-beta
  • PDGFR
  • PDGFR-1
  • PDGFR1
  • Platelet-derived growth factor receptor 1
Gene Name
PDGFRB
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000409|Platelet-derived growth factor receptor beta
MRLPGAMPALALKGELLLLSLLLLLEPQISQGLVVTPPGPELVLNVSSTFVLTCSGSAPV
VWERMSQEPPQEMAKAQDGTFSSVLTLTNLTGLDTGEYFCTHNDSRGLETDERKRLYIFV
PDPTVGFLPNDAEELFIFLTEITEITIPCRVTDPQLVVTLHEKKGDVALPVPYDHQRGFS
GIFEDRSYICKTTIGDREVDSDAYYVYRLQVSSINVSVNAVQTVVRQGENITLMCIVIGN
EVVNFEWTYPRKESGRLVEPVTDFLLDMPYHIRSILHIPSAELEDSGTYTCNVTESVNDH
QDEKAINITVVESGYVRLLGEVGTLQFAELHRSRTLQVVFEAYPPPTVLWFKDNRTLGDS
SAGEIALSTRNVSETRYVSELTLVRVKVAEAGHYTMRAFHEDAEVQLSFQLQINVPVRVL
ELSESHPDSGEQTVRCRGRGMPQPNIIWSACRDLKRCPRELPPTLLGNSSEEESQLETNV
TYWEEEQEFEVVSTLRLQHVDRPLSVRCTLRNAVGQDTQEVIVVPHSLPFKVVVISAILA
LVVLTIISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIYVDPMQLPYDSTWELPRDQL
VLGRTLGSGAFGQVVEATAHGLSHSQATMKVAVKMLKSTARSSEKQALMSELKIMSHLGP
HLNVVNLLGACTKGGPIYIITEYCRYGDLVDYLHRNKHTFLQHHSDKRRPPSAELYSNAL
PVGLPLPSHVSLTGESDGGYMDMSKDESVDYVPMLDMKGDVKYADIESSNYMAPYDNYVP
SAPERTCRATLINESPVLSYMDLVGFSYQVANGMEFLASKNCVHRDLAARNVLICEGKLV
KICDFGLARDIMRDSNYISKGSTFLPLKWMAPESIFNSLYTTLSDVWSFGILLWEIFTLG
GTPYPELPMNEQFYNAIKRGYRMAQPAHASDEIYEIMQKCWEEKFEIRPPFSQLVLLLER
LLGEGYKKKYQQVDEEFLRSDHPAILRSQARLPGFHGLRSPLDTSSVLYTAVQPNEGDND
YIIPLPDPKPEVADEGPLEGSPSLASSTLNEVNTSSTISCDSPLEPQDEPEPEPQLELQV
EPEPELEQLPDSGCPAPRAEAEDSFL
Number of residues
1106
Molecular Weight
123966.895
Theoretical pI
4.62
GO Classification
Functions
ATP binding / platelet activating factor receptor activity / platelet-derived growth factor beta-receptor activity / platelet-derived growth factor binding / platelet-derived growth factor receptor binding / platelet-derived growth factor-activated receptor activity / protein kinase binding / protein tyrosine kinase activity / receptor binding / vascular endothelial growth factor binding
Processes
activation of MAPKK activity / adrenal gland development / aorta morphogenesis / axon guidance / cardiac myofibril assembly / cell chemotaxis / cell migration / cell migration involved in coronary angiogenesis / cell migration involved in vasculogenesis / cellular response to platelet-derived growth factor stimulus / epidermal growth factor receptor signaling pathway / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / G-protein coupled receptor signaling pathway / glycosaminoglycan biosynthetic process / in utero embryonic development / innate immune response / inner ear development / insulin receptor signaling pathway / MAPK cascade / metanephric comma-shaped body morphogenesis / metanephric glomerular capillary formation / metanephric glomerular mesangial cell proliferation involved in metanephros development / metanephric mesenchymal cell migration / metanephric mesenchyme development / metanephric S-shaped body morphogenesis / negative regulation of apoptotic process / neurotrophin TRK receptor signaling pathway / peptidyl-tyrosine phosphorylation / phosphatidylinositol metabolic process / phosphatidylinositol-mediated signaling / platelet-derived growth factor receptor signaling pathway / platelet-derived growth factor receptor-beta signaling pathway / positive regulation of calcium ion import / positive regulation of cell migration / positive regulation of cell proliferation / positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway / positive regulation of chemotaxis / positive regulation of collagen biosynthetic process / positive regulation of DNA biosynthetic process / positive regulation of ERK1 and ERK2 cascade / positive regulation of MAP kinase activity / positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway / positive regulation of mitotic nuclear division / positive regulation of phosphatidylinositol 3-kinase activity / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of phospholipase C activity / positive regulation of phosphoprotein phosphatase activity / positive regulation of reactive oxygen species metabolic process / positive regulation of smooth muscle cell migration / positive regulation of smooth muscle cell proliferation / protein autophosphorylation / Ras protein signal transduction / regulation of actin cytoskeleton organization / regulation of peptidyl-tyrosine phosphorylation / response to estradiol / response to fluid shear stress / response to hydrogen peroxide / response to hyperoxia / response to retinoic acid / response to toxic substance / retina vasculature development in camera-type eye / signal transduction / skeletal system morphogenesis / small GTPase mediated signal transduction / smooth muscle cell chemotaxis / smooth muscle tissue development / tissue homeostasis / vascular endothelial growth factor receptor signaling pathway / wound healing
Components
apical plasma membrane / cell surface / cytoplasm / cytoplasmic membrane-bounded vesicle / extracellular exosome / focal adhesion / integral component of membrane / intrinsic component of plasma membrane / lysosomal lumen / membrane / nucleus / plasma membrane
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -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 PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. 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. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. 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.
Pfam Domain Function
Transmembrane Regions
533-553
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0021922|Platelet-derived growth factor receptor beta (PDGFRB)
ATGCGGCTTCCGGGTGCGATGCCAGCTCTGGCCCTCAAAGGCGAGCTGCTGTTGCTGTCT
CTCCTGTTACTTCTGGAACCACAGATCTCTCAGGGCCTGGTCGTCACACCCCCGGGGCCA
GAGCTTGTCCTCAATGTCTCCAGCACCTTCGTTCTGACCTGCTCGGGTTCAGCTCCGGTG
GTGTGGGAACGGATGTCCCAGGAGCCCCCACAGGAAATGGCCAAGGCCCAGGATGGCACC
TTCTCCAGCGTGCTCACACTGACCAACCTCACTGGGCTAGACACGGGAGAATACTTTTGC
ACCCACAATGACTCCCGTGGACTGGAGACCGATGAGCGGAAACGGCTCTACATCTTTGTG
CCAGATCCCACCGTGGGCTTCCTCCCTAATGATGCCGAGGAACTATTCATCTTTCTCACG
GAAATAACTGAGATCACCATTCCATGCCGAGTAACAGACCCACAGCTGGTGGTGACACTG
CACGAGAAGAAAGGGGACGTTGCACTGCCTGTCCCCTATGATCACCAACGTGGCTTTTCT
GGTATCTTTGAGGACAGAAGCTACATCTGCAAAACCACCATTGGGGACAGGGAGGTGGAT
TCTGATGCCTACTATGTCTACAGACTCCAGGTGTCATCCATCAACGTCTCTGTGAACGCA
GTGCAGACTGTGGTCCGCCAGGGTGAGAACATCACCCTCATGTGCATTGTGATCGGGAAT
GAGGTGGTCAACTTCGAGTGGACATACCCCCGCAAAGAAAGTGGGCGGCTGGTGGAGCCG
GTGACTGACTTCCTCTTGGATATGCCTTACCACATCCGCTCCATCCTGCACATCCCCAGT
GCCGAGTTAGAAGACTCGGGGACCTACACCTGCAATGTGACGGAGAGTGTGAATGACCAT
CAGGATGAAAAGGCCATCAACATCACCGTGGTTGAGAGCGGCTACGTGCGGCTCCTGGGA
GAGGTGGGCACACTACAATTTGCTGAGCTGCATCGGAGCCGGACACTGCAGGTAGTGTTC
GAGGCCTACCCACCGCCCACTGTCCTGTGGTTCAAAGACAACCGCACCCTGGGCGACTCC
AGCGCTGGCGAAATCGCCCTGTCCACGCGCAACGTGTCGGAGACCCGGTATGTGTCAGAG
CTGACACTGGTTCGCGTGAAGGTGGCAGAGGCTGGCCACTACACCATGCGGGCCTTCCAT
GAGGATGCTGAGGTCCAGCTCTCCTTCCAGCTACAGATCAATGTCCCTGTCCGAGTGCTG
GAGCTAAGTGAGAGCCACCCTGACAGTGGGGAACAGACAGTCCGCTGTCGTGGCCGGGGC
ATGCCCCAGCCGAACATCATCTGGTCTGCCTGCAGAGACCTCAAAAGGTGTCCACGTGAG
CTGCCGCCCACGCTGCTGGGGAACAGTTCCGAAGAGGAGAGCCAGCTGGAGACTAACGTG
ACGTACTGGGAGGAGGAGCAGGAGTTTGAGGTGGTGAGCACACTGCGTCTGCAGCACGTG
GATCGGCCACTGTCGGTGCGCTGCACGCTGCGCAACGCTGTGGGCCAGGACACGCAGGAG
GTCATCGTGGTGCCACACTCCTTGCCCTTTAAGGTGGTGGTGATCTCAGCCATCCTGGCC
CTGGTGGTGCTCACCATCATCTCCCTTATCATCCTCATCATGCTTTGGCAGAAGAAGCCA
CGTTACGAGATCCGATGGAAGGTGATTGAGTCTGTGAGCTCTGACGGCCATGAGTACATC
TACGTGGACCCCATGCAGCTGCCCTATGACTCCACGTGGGAGCTGCCGCGGGACCAGCTT
GTGCTGGGACGCACCCTCGGCTCTGGGGCCTTTGGGCAGGTGGTGGAGGCCACGGCTCAT
GGCCTGAGCCATTCTCAGGCCACGATGAAAGTGGCCGTCAAGATGCTTAAATCCACAGCC
CGCAGCAGTGAGAAGCAAGCCCTTATGTCGGAGCTGAAGATCATGAGTCACCTTGGGCCC
CACCTGAACGTGGTCAACCTGTTGGGGGCCTGCACCAAAGGAGGACCCATCTATATCATC
ACTGAGTACTGCCGCTACGGAGACCTGGTGGACTACCTGCACCGCAACAAACACACCTTC
CTGCAGCACCACTCCGACAAGCGCCGCCCGCCCAGCGCGGAGCTCTACAGCAATGCTCTG
CCCGTTGGGCTCCCCCTGCCCAGCCATGTGTCCTTGACCGGGGAGAGCGACGGTGGCTAC
ATGGACATGAGCAAGGACGAGTCGGTGGACTATGTGCCCATGCTGGACATGAAAGGAGAC
GTCAAATATGCAGACATCGAGTCCTCCAACTACATGGCCCCTTACGATAACTACGTTCCC
TCTGCCCCTGAGAGGACCTGCCGAGCAACTTTGATCAACGAGTCTCCAGTGCTAAGCTAC
ATGGACCTCGTGGGCTTCAGCTACCAGGTGGCCAATGGCATGGAGTTTCTGGCCTCCAAG
AACTGCGTCCACAGAGACCTGGCGGCTAGGAACGTGCTCATCTGTGAAGGCAAGCTGGTC
AAGATCTGTGACTTTGGCCTGGCTCGAGACATCATGCGGGACTCGAATTACATCTCCAAA
GGCAGCACCTTTTTGCCTTTAAAGTGGATGGCTCCGGAGAGCATCTTCAACAGCCTCTAC
ACCACCCTGAGCGACGTGTGGTCCTTCGGGATCCTGCTCTGGGAGATCTTCACCTTGGGT
GGCACCCCTTACCCAGAGCTGCCCATGAACGAGCAGTTCTACAATGCCATCAAACGGGGT
TACCGCATGGCCCAGCCTGCCCATGCCTCCGACGAGATCTATGAGATCATGCAGAAGTGC
TGGGAAGAGAAGTTTGAGATTCGGCCCCCCTTCTCCCAGCTGGTGCTGCTTCTCGAGAGA
CTGTTGGGCGAAGGTTACAAAAAGAAGTACCAGCAGGTGGATGAGGAGTTTCTGAGGAGT
GACCACCCAGCCATCCTTCGGTCCCAGGCCCGCTTGCCTGGGTTCCATGGCCTCCGATCT
CCCCTGGACACCAGCTCCGTCCTCTATACTGCCGTGCAGCCCAATGAGGGTGACAACGAC
TATATCATCCCCCTGCCTGACCCCAAACCCGAGGTTGCTGACGAGGGCCCACTGGAGGGT
TCCCCCAGCCTAGCCAGCTCCACCCTGAATGAAGTCAACACCTCCTCAACCATCTCCTGT
GACAGCCCCCTGGAGCCCCAGGACGAACCAGAGCCAGAGCCCCAGCTTGAGCTCCAGGTG
GAGCCGGAGCCAGAGCTGGAACAGTTGCCGGATTCGGGGTGCCCTGCGCCTCGGGCGGAA
GCAGAGGATAGCTTCCTGTAG
Chromosome Location
5
Locus
5q31-q32
External Identifiers
ResourceLink
UniProtKB IDP09619
UniProtKB Entry NamePGFRB_HUMAN
GenBank Protein ID189732
GenBank Gene IDJ03278
GenAtlas IDPDGFRB
HGNC IDHGNC:8804
General References
  1. Gronwald RG, Grant FJ, Haldeman BA, Hart CE, O'Hara PJ, Hagen FS, Ross R, Bowen-Pope DF, Murray MJ: Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: evidence for more than one receptor class. Proc Natl Acad Sci U S A. 1988 May;85(10):3435-9. [PubMed:2835772]
  2. Claesson-Welsh L, Eriksson A, Moren A, Severinsson L, Ek B, Ostman A, Betsholtz C, Heldin CH: cDNA cloning and expression of a human platelet-derived growth factor (PDGF) receptor specific for B-chain-containing PDGF molecules. Mol Cell Biol. 1988 Aug;8(8):3476-86. [PubMed:2850496]
  3. Jin P, Zhang J, Sumariwalla PF, Ni I, Jorgensen B, Crawford D, Phillips S, Feldmann M, Shepard HM, Paleolog EM: Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. Arthritis Res Ther. 2008;10(4):R73. doi: 10.1186/ar2447. Epub 2008 Jul 1. [PubMed:18593464]
  4. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [PubMed:15372022]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  6. Chi KD, McPhee RA, Wagner AS, Dietz JJ, Pantazis P, Goustin AS: Integration of proviral DNA into the PDGF beta-receptor gene in HTLV-I-infected T-cells results in a novel tyrosine kinase product with transforming activity. Oncogene. 1997 Aug 28;15(9):1051-7. [PubMed:9285559]
  7. Chmielecki J, Peifer M, Viale A, Hutchinson K, Giltnane J, Socci ND, Hollis CJ, Dean RS, Yenamandra A, Jagasia M, Kim AS, Dave UP, Thomas RK, Pao W: Systematic screen for tyrosine kinase rearrangements identifies a novel C6orf204-PDGFRB fusion in a patient with recurrent T-ALL and an associated myeloproliferative neoplasm. Genes Chromosomes Cancer. 2012 Jan;51(1):54-65. doi: 10.1002/gcc.20930. Epub 2011 Sep 21. [PubMed:21938754]
  8. Roberts WM, Look AT, Roussel MF, Sherr CJ: Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes. Cell. 1988 Nov 18;55(4):655-61. [PubMed:2846185]
  9. Zhang Z, Henzel WJ: Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004 Oct;13(10):2819-24. Epub 2004 Aug 31. [PubMed:15340161]
  10. Kazlauskas A, Cooper JA: Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins. Cell. 1989 Sep 22;58(6):1121-33. [PubMed:2550144]
  11. Matsui T, Pierce JH, Fleming TP, Greenberger JS, LaRochelle WJ, Ruggiero M, Aaronson SA: Independent expression of human alpha or beta platelet-derived growth factor receptor cDNAs in a naive hematopoietic cell leads to functional coupling with mitogenic and chemotactic signaling pathways. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8314-8. [PubMed:2554309]
  12. Kazlauskas A, Durden DL, Cooper JA: Functions of the major tyrosine phosphorylation site of the PDGF receptor beta subunit. Cell Regul. 1991 Jun;2(6):413-25. [PubMed:1653029]
  13. Kelly JD, Haldeman BA, Grant FJ, Murray MJ, Seifert RA, Bowen-Pope DF, Cooper JA, Kazlauskas A: Platelet-derived growth factor (PDGF) stimulates PDGF receptor subunit dimerization and intersubunit trans-phosphorylation. J Biol Chem. 1991 May 15;266(14):8987-92. [PubMed:1709159]
  14. Sorkin A, Westermark B, Heldin CH, Claesson-Welsh L: Effect of receptor kinase inactivation on the rate of internalization and degradation of PDGF and the PDGF beta-receptor. J Cell Biol. 1991 Feb;112(3):469-78. [PubMed:1846866]
  15. Kashishian A, Kazlauskas A, Cooper JA: Phosphorylation sites in the PDGF receptor with different specificities for binding GAP and PI3 kinase in vivo. EMBO J. 1992 Apr;11(4):1373-82. [PubMed:1314164]
  16. Ronnstrand L, Mori S, Arridsson AK, Eriksson A, Wernstedt C, Hellman U, Claesson-Welsh L, Heldin CH: Identification of two C-terminal autophosphorylation sites in the PDGF beta-receptor: involvement in the interaction with phospholipase C-gamma. EMBO J. 1992 Nov;11(11):3911-9. [PubMed:1396585]
  17. Mori S, Heldin CH, Claesson-Welsh L: Ligand-induced polyubiquitination of the platelet-derived growth factor beta-receptor. J Biol Chem. 1992 Mar 25;267(9):6429-34. [PubMed:1313434]
  18. Kazlauskas A, Kashishian A, Cooper JA, Valius M: GTPase-activating protein and phosphatidylinositol 3-kinase bind to distinct regions of the platelet-derived growth factor receptor beta subunit. Mol Cell Biol. 1992 Jun;12(6):2534-44. [PubMed:1375321]
  19. Mori S, Ronnstrand L, Yokote K, Engstrom A, Courtneidge SA, Claesson-Welsh L, Heldin CH: Identification of two juxtamembrane autophosphorylation sites in the PDGF beta-receptor; involvement in the interaction with Src family tyrosine kinases. EMBO J. 1993 Jun;12(6):2257-64. [PubMed:7685273]
  20. Fretto LJ, Snape AJ, Tomlinson JE, Seroogy JJ, Wolf DL, LaRochelle WJ, Giese NA: Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB binding to alpha and beta PDGF receptor. J Biol Chem. 1993 Feb 15;268(5):3625-31. [PubMed:7679113]
  21. Lechleider RJ, Sugimoto S, Bennett AM, Kashishian AS, Cooper JA, Shoelson SE, Walsh CT, Neel BG: Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor. J Biol Chem. 1993 Oct 15;268(29):21478-81. [PubMed:7691811]
  22. Nishimura R, Li W, Kashishian A, Mondino A, Zhou M, Cooper J, Schlessinger J: Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor. Mol Cell Biol. 1993 Nov;13(11):6889-96. [PubMed:7692233]
  23. Welsh M, Mares J, Karlsson T, Lavergne C, Breant B, Claesson-Welsh L: Shb is a ubiquitously expressed Src homology 2 protein. Oncogene. 1994 Jan;9(1):19-27. [PubMed:8302579]
  24. Yokote K, Margolis B, Heldin CH, Claesson-Welsh L: Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors. J Biol Chem. 1996 Nov 29;271(48):30942-9. [PubMed:8940081]
  25. Abe A, Emi N, Tanimoto M, Terasaki H, Marunouchi T, Saito H: Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution. Blood. 1997 Dec 1;90(11):4271-7. [PubMed:9373237]
  26. Wang J, Dai H, Yousaf N, Moussaif M, Deng Y, Boufelliga A, Swamy OR, Leone ME, Riedel H: Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis. Mol Cell Biol. 1999 Sep;19(9):6217-28. [PubMed:10454568]
  27. Yokouchi M, Wakioka T, Sakamoto H, Yasukawa H, Ohtsuka S, Sasaki A, Ohtsubo M, Valius M, Inoue A, Komiya S, Yoshimura A: APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis. Oncogene. 1999 Jan 21;18(3):759-67. [PubMed:9989826]
  28. Kovalenko M, Denner K, Sandstrom J, Persson C, Gross S, Jandt E, Vilella R, Bohmer F, Ostman A: Site-selective dephosphorylation of the platelet-derived growth factor beta-receptor by the receptor-like protein-tyrosine phosphatase DEP-1. J Biol Chem. 2000 May 26;275(21):16219-26. [PubMed:10821867]
  29. Arcaro A, Zvelebil MJ, Wallasch C, Ullrich A, Waterfield MD, Domin J: Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors. Mol Cell Biol. 2000 Jun;20(11):3817-30. [PubMed:10805725]
  30. Gilbertson DG, Duff ME, West JW, Kelly JD, Sheppard PO, Hofstrand PD, Gao Z, Shoemaker K, Bukowski TR, Moore M, Feldhaus AL, Humes JM, Palmer TE, Hart CE: Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor. J Biol Chem. 2001 Jul 20;276(29):27406-14. Epub 2001 Apr 10. [PubMed:11297552]
  31. Bergsten E, Uutela M, Li X, Pietras K, Ostman A, Heldin CH, Alitalo K, Eriksson U: PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat Cell Biol. 2001 May;3(5):512-6. [PubMed:11331881]
  32. Apperley JF, Gardembas M, Melo JV, Russell-Jones R, Bain BJ, Baxter EJ, Chase A, Chessells JM, Colombat M, Dearden CE, Dimitrijevic S, Mahon FX, Marin D, Nikolova Z, Olavarria E, Silberman S, Schultheis B, Cross NC, Goldman JM: Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med. 2002 Aug 15;347(7):481-7. [PubMed:12181402]
  33. Wilkinson K, Velloso ER, Lopes LF, Lee C, Aster JC, Shipp MA, Aguiar RC: Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib. Blood. 2003 Dec 1;102(12):4187-90. Epub 2003 Aug 7. [PubMed:12907457]
  34. Morerio C, Acquila M, Rosanda C, Rapella A, Dufour C, Locatelli F, Maserati E, Pasquali F, Panarello C: HCMOGT-1 is a novel fusion partner to PDGFRB in juvenile myelomonocytic leukemia with t(5;17)(q33;p11.2). Cancer Res. 2004 Apr 15;64(8):2649-51. [PubMed:15087372]
  35. Grand FH, Burgstaller S, Kuhr T, Baxter EJ, Webersinke G, Thaler J, Chase AJ, Cross NC: p53-Binding protein 1 is fused to the platelet-derived growth factor receptor beta in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder. Cancer Res. 2004 Oct 15;64(20):7216-9. [PubMed:15492236]
  36. Persson C, Savenhed C, Bourdeau A, Tremblay ML, Markova B, Bohmer FD, Haj FG, Neel BG, Elson A, Heldin CH, Ronnstrand L, Ostman A, Hellberg C: Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase. Mol Cell Biol. 2004 Mar;24(5):2190-201. [PubMed:14966296]
  37. Choi MH, Lee IK, Kim GW, Kim BU, Han YH, Yu DY, Park HS, Kim KY, Lee JS, Choi C, Bae YS, Lee BI, Rhee SG, Kang SW: Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II. Nature. 2005 May 19;435(7040):347-53. [PubMed:15902258]
  38. Reddi AL, Ying G, Duan L, Chen G, Dimri M, Douillard P, Druker BJ, Naramura M, Band V, Band H: Binding of Cbl to a phospholipase Cgamma1-docking site on platelet-derived growth factor receptor beta provides a dual mechanism of negative regulation. J Biol Chem. 2007 Oct 5;282(40):29336-47. Epub 2007 Jul 9. [PubMed:17620338]
  39. Ustach CV, Huang W, Conley-LaComb MK, Lin CY, Che M, Abrams J, Kim HR: A novel signaling axis of matriptase/PDGF-D/ss-PDGFR in human prostate cancer. Cancer Res. 2010 Dec 1;70(23):9631-40. doi: 10.1158/0008-5472.CAN-10-0511. Epub 2010 Nov 23. [PubMed:21098708]
  40. Wardega P, Heldin CH, Lennartsson J: Mutation of tyrosine residue 857 in the PDGF beta-receptor affects cell proliferation but not migration. Cell Signal. 2010 Sep;22(9):1363-8. doi: 10.1016/j.cellsig.2010.05.004. Epub 2010 May 18. [PubMed:20494825]
  41. Mendelson K, Swendeman S, Saftig P, Blobel CP: Stimulation of platelet-derived growth factor receptor beta (PDGFRbeta) activates ADAM17 and promotes metalloproteinase-dependent cross-talk between the PDGFRbeta and epidermal growth factor receptor (EGFR) signaling pathways. J Biol Chem. 2010 Aug 6;285(32):25024-32. doi: 10.1074/jbc.M110.102566. Epub 2010 Jun 7. [PubMed:20529858]
  42. Kim HJ, Cha BY, Choi B, Lim JS, Woo JT, Kim JS: Glyceollins inhibit platelet-derived growth factor-mediated human arterial smooth muscle cell proliferation and migration. Br J Nutr. 2012 Jan;107(1):24-35. doi: 10.1017/S0007114511002571. Epub 2011 Jun 29. [PubMed:21733313]
  43. Yokote K, Mori S, Hansen K, McGlade J, Pawson T, Heldin CH, Claesson-Welsh L: Direct interaction between Shc and the platelet-derived growth factor beta-receptor. J Biol Chem. 1994 May 27;269(21):15337-43. [PubMed:8195171]
  44. Caglayan E, Vantler M, Leppanen O, Gerhardt F, Mustafov L, Ten Freyhaus H, Kappert K, Odenthal M, Zimmermann WH, Tallquist MD, Rosenkranz S: Disruption of platelet-derived growth factor-dependent phosphatidylinositol 3-kinase and phospholipase Cgamma 1 activity abolishes vascular smooth muscle cell proliferation and migration and attenuates neointima formation in vivo. J Am Coll Cardiol. 2011 Jun 21;57(25):2527-38. doi: 10.1016/j.jacc.2011.02.037. [PubMed:21679854]
  45. Heldin CH, Ostman A, Ronnstrand L: Signal transduction via platelet-derived growth factor receptors. Biochim Biophys Acta. 1998 Aug 19;1378(1):F79-113. [PubMed:9739761]
  46. Ostman A: PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Cytokine Growth Factor Rev. 2004 Aug;15(4):275-86. [PubMed:15207817]
  47. Ostman A, Heldin CH: PDGF receptors as targets in tumor treatment. Adv Cancer Res. 2007;97:247-74. [PubMed:17419949]
  48. Andrae J, Gallini R, Betsholtz C: Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008 May 15;22(10):1276-312. doi: 10.1101/gad.1653708. [PubMed:18483217]
  49. Pauptit RA, Dennis CA, Derbyshire DJ, Breeze AL, Weston SA, Rowsell S, Murshudov GN: NMR trial models: experiences with the colicin immunity protein Im7 and the p85alpha C-terminal SH2-peptide complex. Acta Crystallogr D Biol Crystallogr. 2001 Oct;57(Pt 10):1397-404. Epub 2001 Sep 21. [PubMed:11567151]
  50. Karthikeyan S, Leung T, Ladias JA: Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors. J Biol Chem. 2002 May 24;277(21):18973-8. Epub 2002 Mar 6. [PubMed:11882663]
  51. Shim AH, Liu H, Focia PJ, Chen X, Lin PC, He X: Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex. Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11307-12. doi: 10.1073/pnas.1000806107. Epub 2010 Jun 2. [PubMed:20534510]
  52. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846]
  53. Martignetti JA, Tian L, Li D, Ramirez MC, Camacho-Vanegas O, Camacho SC, Guo Y, Zand DJ, Bernstein AM, Masur SK, Kim CE, Otieno FG, Hou C, Abdel-Magid N, Tweddale B, Metry D, Fournet JC, Papp E, McPherson EW, Zabel C, Vaksmann G, Morisot C, Keating B, Sleiman PM, Cleveland JA, Everman DB, Zackai E, Hakonarson H: Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. Am J Hum Genet. 2013 Jun 6;92(6):1001-7. doi: 10.1016/j.ajhg.2013.04.024. Epub 2013 May 23. [PubMed:23731542]
  54. Cheung YH, Gayden T, Campeau PM, LeDuc CA, Russo D, Nguyen VH, Guo J, Qi M, Guan Y, Albrecht S, Moroz B, Eldin KW, Lu JT, Schwartzentruber J, Malkin D, Berghuis AM, Emil S, Gibbs RA, Burk DL, Vanstone M, Lee BH, Orchard D, Boycott KM, Chung WK, Jabado N: A recurrent PDGFRB mutation causes familial infantile myofibromatosis. Am J Hum Genet. 2013 Jun 6;92(6):996-1000. doi: 10.1016/j.ajhg.2013.04.026. Epub 2013 May 23. [PubMed:23731537]
  55. Nicolas G, Pottier C, Maltete D, Coutant S, Rovelet-Lecrux A, Legallic S, Rousseau S, Vaschalde Y, Guyant-Marechal L, Augustin J, Martinaud O, Defebvre L, Krystkowiak P, Pariente J, Clanet M, Labauge P, Ayrignac X, Lefaucheur R, Le Ber I, Frebourg T, Hannequin D, Campion D: Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification. Neurology. 2013 Jan 8;80(2):181-7. doi: 10.1212/WNL.0b013e31827ccf34. Epub 2012 Dec 19. [PubMed:23255827]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00102Becaplerminapproved, investigationalyesDetails
DB00619ImatinibapprovedunknownantagonistDetails
DB00398Sorafenibapproved, investigationalyesantagonistDetails
DB01254Dasatinibapproved, investigationalunknownantagonistDetails
DB01268Sunitinibapproved, investigationalyesinhibitorDetails
DB05014XL999investigationalunknownDetails
DB05146XL820investigationalunknownDetails
DB06589PazopanibapprovedyesinhibitorDetails
DB06595Midostaurinapproved, investigationalyesantagonistinhibitorDetails
DB08896RegorafenibapprovedyesinhibitorDetails
DB09221PolaprezincexperimentalunknownagonistDetails
DB10770Foreskin fibroblast (neonatal)approvedunknownagonistDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB12147Erdafitinibapproved, investigationalunknownsubstrateDetails