P05622 (PGFRB_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 155. History...
Names and origin
|Protein names||Recommended name:|
Platelet-derived growth factor receptor beta
Beta platelet-derived growth factor receptor
Beta-type platelet-derived growth factor receptor
CD140 antigen-like family member B
Platelet-derived growth factor receptor 1
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||1098 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 Ca2+ 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 By similarity. 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. Ref.2 Ref.6 Ref.8 Ref.9 Ref.11 Ref.12 Ref.14 Ref.16 Ref.17
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.8
Present in an inactive conformation in the absence of bound ligand. Binding of PDGFB and/or PDGFD leads to dimerization and activation by autophosphorylation on tyrosine residues.
Interacts with homodimeric PDGFB and PDGFD, and with heterodimers formed by PDGFA and PDGFB. May also interact with homodimeric PDGFC. Monomer in the absence of bound ligand. Interaction with homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD, leads to receptor dimerization, where both PDGFRA homodimers and heterodimers with PDGFRB are observed. Interacts with SH2B2/APS. Interacts directly (tyrosine phosphorylated) with SHB. Interacts (tyrosine phosphorylated) with PIK3R1. Interacts (tyrosine phosphorylated) with CBL. Interacts (tyrosine phosphorylated) with SRC and SRC family kinases. Interacts (tyrosine phosphorylated) with PIK3C2B, maybe indirectly. Interacts (tyrosine phosphorylated) with SHC1, GRB7, GRB10 and NCK1. Interaction with GRB2 is mediated by SHC1. Interacts (via C-terminus) with SLC9A3R1 By similarity. Ref.2 Ref.4 Ref.8 Ref.10 Ref.11 Ref.16 Ref.18
Cell membrane; Single-pass type I membrane protein. Cytoplasmic vesicle By similarity. Lysosome lumen By similarity. Note: After ligand binding, the autophosphorylated receptor is ubiquitinated and internalized, leading to its degradation.
Weakly expressed in glomerular mesangial cells and interstitial cells. Up-regulated in areas of renal fibrosis. In mice with unilateral ureteral obstruction, increased expression in interstitial cells at day 4 and expression is markedly elevated at day 7 and is maximal at day 14. Ref.5
Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-578, and to a lesser degree, Tyr-580 is important for interaction with SRC. Phosphorylation at Tyr-715 is important for interaction with GRB2. Phosphorylation at Tyr-739 and Tyr-750 is important for interaction with PIK3R1. Phosphorylation at Tyr-750 is important for interaction with NCK1. Phosphorylation at Tyr-770 and Tyr-856 is important for interaction with RASA1/GAP. Phosphorylation at Tyr-856 is important for efficient phosphorylation of PLCG1 and PTPN11, resulting in increased phosphorylation of AKT1, MAPK1/ERK2 and/or MAPK3/ERK1, PDCD6IP/ALIX and STAM, and in increased cell proliferation. Phosphorylation at Tyr-1008 is important for interaction with PTPN11. Phosphorylation at Tyr-1008 and Tyr-1020 is important for interaction with PLCG1. Dephosphorylated by PTPRJ at Tyr-750, Tyr-856, Tyr-1008 and Tyr-1020 By similarity. Ref.2 Ref.9
N-glycosylated By similarity.
Ubiquitinated. After autophosphorylation, the receptor is polyubiquitinated, leading to its degradation. Ref.10
No apparent phenotype up to 16 dpc. Lethality late during gestation or at birth, due to widespread bleedings. This is due to a severe shortage of vascular smooth muscle cells and pericytes, especially in the central nervous system, skin, lung and heart. Mutants suffer from hemorrhages, anemia, thrombocytopenia, and show defects in the formation of kidney glomeruli, due to a lack of mesangial cells. Ref.3 Ref.7 Ref.13
Contains 5 Ig-like C2-type (immunoglobulin-like) domains.
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Signal peptide||1 – 31||31|
|Chain||32 – 1098||1067||Platelet-derived growth factor receptor beta||PRO_0000016758|
|Topological domain||32 – 531||500||Extracellular Potential|
|Transmembrane||532 – 552||21||Helical; Potential|
|Topological domain||553 – 1098||546||Cytoplasmic Potential|
|Domain||33 – 119||87||Ig-like C2-type 1|
|Domain||128 – 209||82||Ig-like C2-type 2|
|Domain||213 – 308||96||Ig-like C2-type 3|
|Domain||330 – 402||73||Ig-like C2-type 4|
|Domain||415 – 523||109||Ig-like C2-type 5|
|Domain||599 – 961||363||Protein kinase|
|Nucleotide binding||605 – 613||9||ATP By similarity|
|Active site||825||1||Proton acceptor By similarity|
|Binding site||633||1||ATP By similarity|
Amino acid modifications
|Modified residue||561||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||578||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||580||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||588||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||685||1||Phosphotyrosine; by ABL1 and ABL2 Ref.9|
|Modified residue||715||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||739||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||750||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||762||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||770||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||774||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||777||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||856||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||933||1||Phosphotyrosine; by ABL1 and ABL2 Ref.9|
|Modified residue||969||1||Phosphotyrosine; by ABL1 and ABL2 Ref.9|
|Modified residue||1008||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||1020||1||Phosphotyrosine; by autocatalysis By similarity|
|Glycosylation||44||1||N-linked (GlcNAc...) Potential|
|Glycosylation||88||1||N-linked (GlcNAc...) Potential|
|Glycosylation||102||1||N-linked (GlcNAc...) Potential|
|Glycosylation||214||1||N-linked (GlcNAc...) Potential|
|Glycosylation||291||1||N-linked (GlcNAc...) Potential|
|Glycosylation||306||1||N-linked (GlcNAc...) Ref.15|
|Glycosylation||312||1||N-linked (GlcNAc...) Ref.15|
|Glycosylation||353||1||N-linked (GlcNAc...) Potential|
|Glycosylation||370||1||N-linked (GlcNAc...) Potential|
|Glycosylation||444||1||N-linked (GlcNAc...) Potential|
|Glycosylation||467||1||N-linked (GlcNAc...) Ref.15|
|Glycosylation||478||1||N-linked (GlcNAc...) Ref.15|
|Disulfide bond||53 ↔ 99||By similarity|
|Disulfide bond||148 ↔ 189||By similarity|
|Disulfide bond||234 ↔ 290||By similarity|
|Disulfide bond||435 ↔ 507||By similarity|
|Mutagenesis||578||1||Y → F: Strongly reduced levels of vascular smooth muscle cells and pericytes in developing blood vessels; when associated with F-715; F-739; F-750; F-770; F-1008 and F-1020. Ref.6|
|Mutagenesis||715||1||Y → F: Strongly reduced levels of vascular smooth muscle cells and pericytes in developing blood vessels; when associated with F-578; F-739; F-750; F-770; F-1008 and F-1020. Ref.6|
|Mutagenesis||739||1||Y → F: Strongly reduced levels of vascular smooth muscle cells and pericytes in developing blood vessels; when associated with F-578; F-715; F-750; F-770; F-1008 and F-1020. Ref.6|
|Mutagenesis||750||1||Y → F: Strongly reduced levels of vascular smooth muscle cells and pericytes in developing blood vessels; when associated with F-578; F-715; F-739; F-770; F-1008 and F-1020. Ref.6|
|Mutagenesis||770||1||Y → F: Strongly reduced levels of vascular smooth muscle cells and pericytes in developing blood vessels; when associated with F-578; F-715; F-739; F-750; F-1008 and F-1020. Ref.6|
|Mutagenesis||849||1||D → N: Increased autophosphorylation in the absence of PDGFB binding. Increased autophosphorylation in response to PDGFB binding. Constitutive interaction with PIK3R1, and constitutive AKT1 activation. Ref.8|
|Mutagenesis||1008||1||Y → F: Strongly reduced levels of vascular smooth muscle cells and pericytes in developing blood vessels; when associated with F-578; F-715; F-739; F-750; F-770 and F-1020. Ref.6|
|Mutagenesis||1020||1||Y → F: Strongly reduced levels of vascular smooth muscle cells and pericytes in developing blood vessels; when associated with F-578; F-715; F-739; F-750; F-770 and F-1008. Ref.6|
|||"Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors."|
Yarden Y., Escobedo J.A., Kuang W.-J., Yang-Feng T.L., Daniel T.O., Tremble P.M., Chen E.Y., Ando M.E., Harkins R.N., Francke U., Fried V.A., Ullrich A., Williams L.T.
Nature 323:226-232(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
|||"PDGF-AB requires PDGF receptor alpha-subunits for high-affinity, but not for low-affinity, binding and signal transduction."|
Seifert R.A., van Koppen A., Bowen-Pope D.F.
J. Biol. Chem. 268:4473-4480(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS RECEPTOR FOR PDGFA AND PDGFB, SUBUNIT, AUTOPHOSPHORYLATION.
|||"Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice."|
Genes Dev. 8:1888-1896(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
|||"Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis."|
Wang J., Dai H., Yousaf N., Moussaif M., Deng Y., Boufelliga A., Swamy O.R., Leone M.E., Riedel H.
Mol. Cell. Biol. 19:6217-6228(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRB10.
|||"Obstructive uropathy in mice and humans: potential role for PDGF-D in the progression of tubulointerstitial injury."|
Taneda S., Hudkins K.L., Topouzis S., Gilbertson D.G., Ophascharoensuk V., Truong L., Johnson R.J., Alpers C.E.
J. Am. Soc. Nephrol. 14:2544-2555(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
|||"Additive effects of PDGF receptor beta signaling pathways in vascular smooth muscle cell development."|
Tallquist M.D., French W.J., Soriano P.
PLoS Biol. 1:E52-E52(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF TYR-578; TYR-715; TYR-739; TYR-750; TYR-770; TYR-1008 AND TYR-1020.
|||"Insight into the physiological functions of PDGF through genetic studies in mice."|
Cytokine Growth Factor Rev. 15:215-228(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, DISRUPTION PHENOTYPE.
|||"A gain of function mutation in the activation loop of platelet-derived growth factor beta-receptor deregulates its kinase activity."|
Chiara F., Goumans M.J., Forsberg H., Ahgren A., Rasola A., Aspenstrom P., Wernstedt C., Hellberg C., Heldin C.H., Heuchel R.
J. Biol. Chem. 279:42516-42527(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ASP-849, CATALYTIC ACTIVITY, FUNCTION, INTERACTION WITH PIK3R1.
|||"Bidirectional signaling links the Abelson kinases to the platelet-derived growth factor receptor."|
Plattner R., Koleske A.J., Kazlauskas A., Pendergast A.M.
Mol. Cell. Biol. 24:2573-2583(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT TYR-685; TYR-933 AND TYR-969.
|||"Low density lipoprotein receptor-related protein 1 (LRP1) controls endocytosis and c-CBL-mediated ubiquitination of the platelet-derived growth factor receptor beta (PDGFR beta)."|
Takayama Y., May P., Anderson R.G., Herz J.
J. Biol. Chem. 280:18504-18510(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBL, UBIQUITINATION.
|||"Binding of Cbl to a phospholipase Cgamma1-docking site on platelet-derived growth factor receptor beta provides a dual mechanism of negative regulation."|
Reddi A.L., Ying G., Duan L., Chen G., Dimri M., Douillard P., Druker B.J., Naramura M., Band V., Band H.
J. Biol. Chem. 282:29336-29347(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBL AND PLCG1, FUNCTION.
|||"Platelet-derived growth factor receptor beta signaling is required for efficient epicardial cell migration and development of two distinct coronary vascular smooth muscle cell populations."|
Mellgren A.M., Smith C.L., Olsen G.S., Eskiocak B., Zhou B., Kazi M.N., Ruiz F.R., Pu W.T., Tallquist M.D.
Circ. Res. 103:1393-1401(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"PDGF-B signaling is important for murine cardiac development: its role in developing atrioventricular valves, coronaries, and cardiac innervation."|
Van den Akker N.M., Winkel L.C., Nisancioglu M.H., Maas S., Wisse L.J., Armulik A., Poelmann R.E., Lie-Venema H., Betsholtz C., Gittenberger-de Groot A.C.
Dev. Dyn. 237:494-503(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
|||"Comprehensive dissection of PDGF-PDGFR signaling pathways in PDGFR genetically defined cells."|
Wu E., Palmer N., Tian Z., Moseman A.P., Galdzicki M., Wang X., Berger B., Zhang H., Kohane I.S.
PLoS ONE 3:E3794-E3794(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"The mouse C2C12 myoblast cell surface N-linked glycoproteome: identification, glycosite occupancy, and membrane orientation."|
Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D., Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.
Mol. Cell. Proteomics 8:2555-2569(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-306; ASN-312; ASN-467 AND ASN-478, MASS SPECTROMETRY.
|||"LRP1 regulates architecture of the vascular wall by controlling PDGFRbeta-dependent phosphatidylinositol 3-kinase activation."|
Zhou L., Takayama Y., Boucher P., Tallquist M.D., Herz J.
PLoS ONE 4:E6922-E6922(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PIK3R1.
|||"PDGFRbeta signaling regulates mural cell plasticity and inhibits fat development."|
Olson L.E., Soriano P.
Dev. Cell 20:815-826(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Crystal structures of peptide complexes of the amino-terminal SH2 domain of the Syp tyrosine phosphatase."|
Lee C.-H., Kominos D., Jacques S., Margolis B., Schlessinger J., Shoelson S.E., Kuriyan J.
Structure 2:423-438(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 1005-1015 IN COMPLEX WITH PTPN11, INTERACTION WITH PTPN11.
|+||Additional computationally mapped references.|
|X04367 mRNA. Translation: CAA27882.1.|
|PIR||PFMSRB. A25742. |
|RefSeq||NP_001139740.1. NM_001146268.1. |
3D structure databases
|SMR||P05622. Positions 32-450, 525-562, 575-1007. |
Protein-protein interaction databases
|IntAct||P05622. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|UCSC||uc008fbk.2. mouse. |
|MGI||MGI:97531. Pdgfrb. |
Enzyme and pathway databases
|BRENDA||22.214.171.124. 3474. |
Gene expression databases
|GermOnline||ENSMUSG00000024620. Mus musculus. |
Family and domain databases
|Gene3D||126.96.36.199. 5 hits. |
|InterPro||IPR007110. Ig-like_dom. |
|Pfam||PF00047. ig. 1 hit. |
PF07714. Pkinase_Tyr. 1 hit.
|PIRSF||PIRSF500948. Beta-PDGF_receptor. 1 hit. |
PIRSF000615. TyrPK_CSF1-R. 1 hit.
|PRINTS||PR01832. VEGFRECEPTOR. |
|SMART||SM00409. IG. 1 hit. |
SM00408. IGc2. 1 hit.
SM00219. TyrKc. 1 hit.
|SUPFAM||SSF56112. Kinase_like. 1 hit. |
|PROSITE||PS50835. IG_LIKE. 3 hits. |
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
|Accession||Primary (citable) accession number: P05622|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
|Human and mouse protein kinases|
Human and mouse protein kinases: classification and index
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
Index of Protein Data Bank (PDB) cross-references
Index of protein domains and families