View source for PDGFRB

{{short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Platelet-derived growth factor receptor beta''' is a [[protein]] that in humans is encoded by the ''PDGFRB'' [[gene]]. Mutations in PDGFRB are mainly associated with the [[clonal eosinophilia]] class of malignancies.
== Gene ==
The ''PDGFRB'' gene is located on [[chromosome 5 (human)|human chromosome 5]] at position q32 (designated as 5q32) and contains 25 [[exons]]. The gene is flanked by the genes for [[granulocyte-macrophage colony-stimulating factor]] and [[Colony stimulating factor 1 receptor]] (also termed macrophage-colony stimulating factor receptor), all three of which may be lost together by a  single [[Deletion (genetics)|deletional mutation]] thereby causing development of the [[Myelodysplastic syndrome#5q-syndrome|5q-syndrome]].<ref name="ncbi.nlm.nih.gov">{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/5159 | title=PDGFRB platelet derived growth factor receptor beta &#91;Homo sapiens (human)&#93; - Gene - NCBI}}</ref> Other genetic abnormalities in ''PDGFRB'' lead to various forms of potentially malignant bone marrow disorders: small deletions in and chromosome [[Chromosomal translocation|translocation]]s causing fusions between ''PDGFRB'' and any one of at least 30 genes can cause [[Myeloproliferative neoplasm]]s that commonly involve [[eosinophilia]], eosinophil-induced organ injury, and possible progression to aggressive leukemia (see blow).<ref name="pmid28028030">{{cite journal | vauthors = Reiter A, Gotlib J | title = Myeloid neoplasms with eosinophilia | journal = Blood | volume = 129 | issue = 6 | pages = 704–714 | year = 2017 | pmid = 28028030 | doi = 10.1182/blood-2016-10-695973 | doi-access = free }}</ref>
== Structure ==
The PDGFRB gene encodes a typical [[receptor tyrosine kinase]], which belongs to the type III [[Receptor tyrosine kinase|tyrosine kinase receptor (RTK) family]] and is structurally characterized by five extracellular immunoglobulin-like domains, a single membrane-spanning helix domain, an intracellular juxtamembrane domain, a split tyrosine kinase domain and a carboxylic tail.<ref>{{cite journal | vauthors = Heldin CH, Lennartsson J | title = Structural and functional properties of platelet-derived growth factor and stem cell factor receptors | journal = Cold Spring Harbor Perspectives in Biology | volume = 5 | issue = 8 | pages = a009100 | date = August 2013 | pmid = 23906712 | pmc = 3721287 | doi = 10.1101/cshperspect.a009100 }}</ref> In the absence of ligand, PDGFRβ adopts an inactive conformation in which the activation loop folds over the catalytic site, the juxtamembrane region over a loop occluding the active site and the carboxy-terminal tail over the kinase domain. Upon PDGF binding the dimerization of receptor releases the inhibitory conformations due to auto-phosphorylation of regulatory tyrosine residues in trans fashion. Tyrosine residues 857 and 751 are major phosphorylation sites for the activation of PDGFRβ.<ref>{{cite journal | vauthors = Kelly JD, Haldeman BA, Grant FJ, Murray MJ, Seifert RA, Bowen-Pope DF, Cooper JA, Kazlauskas A | display-authors = 6 | title = Platelet-derived growth factor (PDGF) stimulates PDGF receptor subunit dimerization and intersubunit trans-phosphorylation | journal = The Journal of Biological Chemistry | volume = 266 | issue = 14 | pages = 8987–92 | date = May 1991 | doi = 10.1016/S0021-9258(18)31541-2 | pmid = 1709159 | doi-access = free }}</ref>
The molecular mass of the mature, glycosylated PDGFRβ protein is approximately 180 kDa.
== Modes of activation ==
Activation of PDGFRβ requires de-repression of the receptor's kinase activity.  The ligand for PDGFRβ (PDGF) accomplishes this in the course of assembling a PDGFRβ dimer.  Two of the five PDGF isoforms activate PDGFRβ (PDGF-B and PDGF-D).  The activated receptor phosphorylates itself and other proteins, and thereby engages intracellular signaling pathways that trigger cellular responses such as migration and proliferation. There are also PDGF-independent modes of de-repressing the PDGFRβ's kinase activity and hence activating it.  For instance, forcing PDGFRβ into close proximity of each other by overexpression or with antibodies directed against the extracellular domain.  Alternatively, mutations in the kinase domain that stabilize a kinase active conformation result in constitutive activation.
Unlike PDGFRα, PDGFRβ cannot be indirectly activated. This is because PDGFRβ recruits RasGAP and thereby attenuates Ras/PI3K activity, which is required to engage a feed-forward loop that is responsible for this mode of activation.<ref name="Lei_2014">{{cite journal | vauthors = Lei H, Kazlauskas A | title = A reactive oxygen species-mediated, self-perpetuating loop persistently activates platelet-derived growth factor receptor α | journal = Molecular and Cellular Biology | volume = 34 | issue = 1 | pages = 110–22 | year = 2014 | pmid = 24190966 | pmc = 3911282 | doi = 10.1128/MCB.00839-13 }}</ref><ref name="Lei_2015">{{cite journal | vauthors = Lei H, Qian CX, Lei J, Haddock LJ, Mukai S, Kazlauskas A | title = RasGAP Promotes Autophagy and Thereby Suppresses Platelet-Derived Growth Factor Receptor-Mediated Signaling Events, Cellular Responses, and Pathology | journal = Molecular and Cellular Biology | volume = 35 | issue = 10 | pages = 1673–85 | year = 2015 | pmid = 25733681 | pmc = 4405646 | doi = 10.1128/MCB.01248-14  }}</ref>
== Role in physiology/pathology ==
The phenotype of knock out mice demonstrates that PDGFRB is essential for vascular development, and that PDGFRB is responsible for activating PDGFRβ during embryogenesis.  Eliminating either PDGFRB, or PDGF-B reduces the number of pericytes and vascular smooth muscle cells, and thereby compromises the integrity and/or functionality of the vasculature in multiple organs, including the brain, heart, kidney, skin and eye.<ref name="Soriano_1994">{{cite journal | vauthors = Soriano P | title = Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice | journal = Genes & Development | volume = 8 | issue = 16 | pages = 1888–96 | year = 1994 | pmid = 7958864 | doi = 10.1101/gad.8.16.1888| doi-access = free }}</ref><ref name="Lindahl_1997">{{cite journal | vauthors = Lindahl P, Johansson BR, Levéen P, Betsholtz C | title = Pericyte loss and microaneurysm formation in PDGF-B-deficient mice | journal = Science  | volume = 277 | issue = 5323 | pages = 242–5 | year = 1997 | pmid = 9211853 | doi = 10.1126/science.277.5323.242}}</ref><ref name="Lindahl_1998">{{cite journal | vauthors = Lindahl P, Hellström M, Kalén M, Karlsson L, Pekny M, Pekna M, Soriano P, Betsholtz C | title = Paracrine PDGF-B/PDGF-Rbeta signaling controls mesangial cell development in kidney glomeruli | journal = Development | volume = 125 | issue = 17 | pages = 3313–22 | year = 1998 | doi = 10.1242/dev.125.17.3313 | pmid = 9693135 }}</ref><ref name="Levéen_1994">{{cite journal | vauthors = Levéen P, Pekny M, Gebre-Medhin S, Swolin B, Larsson E, Betsholtz C | title = Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities | journal = Genes & Development | volume = 8 | issue = 16 | pages = 1875–87 | year = 1994 | pmid = 7958863 | doi = 10.1101/gad.8.16.1875| doi-access = free }}</ref>
In vitro studies using cultured cells indicate that endothelial cells secrete PDGF, which recruits PDGFRβ-expressing pericytes that stabilize nascent blood vessels.<ref name="Darland_1999">{{cite journal | vauthors = Darland DC, D'Amore PA | title = Blood vessel maturation: vascular development comes of age | journal = The Journal of Clinical Investigation | volume = 103 | issue = 2 | pages = 157–8 | year = 1999 | pmid = 9916126 | pmc = 407889 | doi = 10.1172/JCI6127 }}</ref>  Mice harboring a single activated allele of PDGFRB show a number of postnatal phenotypes including reduced differentiation of aortic vascular smooth muscle cells and brain pericytes.  Similarly, differentiation of adipose from pericytes and [[mesenchyme|mesenchymal]] cells is suppressed.<ref name="Olson_2011">{{cite journal | vauthors = Olson LE, Soriano P | title = PDGFRβ signaling regulates mural cell plasticity and inhibits fat development | journal = Developmental Cell | volume = 20 | issue = 6 | pages = 815–26 | year = 2011 | pmid = 21664579 | pmc = 3121186 | doi = 10.1016/j.devcel.2011.04.019 }}</ref>  Misregulation of the PDGFRβ's kinase activity (typically activation) contributes to endemic diseases such as cancer and cardiovascular disease.<ref name="Andrae_2008">{{cite journal | vauthors = Andrae J, Gallini R, Betsholtz C | title = Role of platelet-derived growth factors in physiology and medicine | journal = Genes & Development | volume = 22 | issue = 10 | pages = 1276–312 | year = 2008 | pmid = 18483217 | pmc = 2732412 | doi = 10.1101/gad.1653708 }}</ref><ref name="Heldin_2013">{{cite journal | vauthors = Heldin CH | title = Targeting the PDGF signaling pathway in tumor treatment | journal = Cell Communication and Signaling | volume = 11 | pages = 97 | year = 2013 | pmid = 24359404 | pmc = 3878225 | doi = 10.1186/1478-811X-11-97 | doi-access = free }}</ref><ref name="pmid23793451">{{cite journal | vauthors = Heldin CH | title = Targeting the PDGF signaling pathway in the treatment of non-malignant diseases | journal = Journal of Neuroimmune Pharmacology | volume = 9 | issue = 2 | pages = 69–79 | year = 2014 | pmid = 23793451 | doi = 10.1007/s11481-013-9484-2 | s2cid = 17343813 }}</ref>
=== PDGFRB mutations ===
==== 5q- Syndrome ====
Human chromosome 5 deletions that remove three adjacent genes, those for [[granulocyte-macrophage colony-stimulating factor]], PDGFRB, and [[Colony stimulating factor 1 receptor]], cause the [[Chromosome 5q deletion syndrome]] (5q- syndrome). This syndrome is a unique type of [[myelodysplastic syndrome]] characterized by a prolonged disease course, a low rate of transformation to an aggressive form of [[leukemia]], and an [[anemia]] which in many patients is profound, refractory to traditional therapies (e.g. iron supplements, [[Erythropoietin]]), and requiring maintenance red blood cell transfusions. The disease is treated with a [[chemotherapy drug]], [[lenalidomide#Myelodysplastic syndromes|lenalidomide]].<ref name="ncbi.nlm.nih.gov"/><ref name="pmid16735711">{{cite journal | vauthors = Nimer SD | title = Clinical management of myelodysplastic syndromes with interstitial deletion of chromosome 5q | journal = Journal of Clinical Oncology | volume = 24 | issue = 16 | pages = 2576–82 | year = 2006 | pmid = 16735711 | doi = 10.1200/JCO.2005.03.6715 }}</ref>
==== ''PDGFRB'' Translocations ====
Human chromosome translocations between the ''PDGFRB'' gene and at least any one of 30 genes on other chromosomes lead to [[myeloid]] and/or [[lymphoid]] neoplasms that are many ways similar to the neoplasm caused by the fusion of the [[PDGFRA]] (i.e. platelet derived growth factor receptor A or alpha-type-platelet derived growth factor receptor) gene with the [[FIP1L1]] gene (see [[FIP1L1#FIP1L1-PDGFRA|FIP1L1-PDGFRA fusion gene]]. The most common of these rare mutations is the translocation of ''PDGFRB'' gene with the ''[[ETV6]]'' gene (also termed ''ETS variant gene 6'').
===== ''PDGFRB''-''ETV6'' translocations =====
The ''ETV6'' gene codes for a transcription factor protein that in mice appears to be required for [[hematopoiesis]] and maintenance of the developing vascular network. The gene is located on human chromosome 12 at the p13 position, consists of 14 [[exons]], and is well-known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital [[fibrosarcoma]].<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/2120 | title=ETV6 ETS variant 6 &#91;Homo sapiens (human)&#93; - Gene - NCBI}}</ref> Translocations between it and the ''PDGFRB'' gene, notated as t(5;12)(q33;p13), yield a ''PDGFRB-ETV6'' fused gene that encodes a [[fusion protein]], PDGFRB-ETV6. This chimeric protein, unlike the PDGFRB protein: '''a)''' has continuously active PDGFRB-mediated [[tyrosine kinase]] due to its forced dimerization by the PNT protein binding domain of the ETV6 protein; '''b)''' is highly stable due to its resistance to ubiquitin-[[Proteasome]] degradation; and '''c)''' therefore over-stimulates [[cell signaling]] pathways such as [[STAT5]], [[NF-κB]], and [[Extracellular signal-regulated kinases]] which promote cell growth and proliferation. This continuous signaling, it is presumed, leads to the development of myeloid and/or lymphoid neoplasms that commonly include increased numbers of blood born and tissue [[eosinophil]]s, eosinophil-induced organ and tissue injury, and possible progression to aggressive form of leukemia.<ref name="pmid26276769">{{cite journal | vauthors = Vega F, Medeiros LJ, Bueso-Ramos CE, Arboleda P, Miranda RN | title = Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1 | journal = American Journal of Clinical Pathology | volume = 144 | issue = 3 | pages = 377–92 | year = 2015 | pmid = 26276769 | doi = 10.1309/AJCPMORR5Z2IKCEM | doi-access = free }}</ref>
PDGFRB-ETV6 fusion protein-induced neoplasms often present with features that would classify them as [[Chronic myelomonocytic leukemia]]s, [[juvenile myelomonocytic leukemia]], [[Atypical chronic myeloid leukemia|Atypical]] or [[Chronic myelogenous leukemia#Diagnosis|Philadelphia chromosome negative]] chronic myeloid leukemias, [[myelodysplastic syndrome]]s, [[acute myelogenous leukemia]]s, or [[acute lymphoblastic leukemia]]s. The disease is now classified by the World Health Organization as one form of [[clonal eosinophilia]].<ref name="pmid27069254">{{cite journal | vauthors = Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW | title = The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia | journal = Blood | volume = 127 | issue = 20 | pages = 2391–405 | year = 2016 | pmid = 27069254 | doi = 10.1182/blood-2016-03-643544 | doi-access = free }}</ref> It is critical that the PDGFRB-ETV6 fusion protein-driven disease be diagnostically distinguished from many of the just cited other diseases because of its very different treatment.
Patients with the PDGFRB-ETV6 fusion protein-driven disease are more often adult males but rarely children. They present with [[anemia]], increases in blood eosinophils and monocytes, [[splenomegaly]], and, less often, lymphadenopathy. [[Bone marrow examination]] may reveal cellular features similar to that seen in the aforementioned diseases. Diagnosis is may by conventional [[cytogenetic]] examination of blood or bone marrow cells to test for PDGFRB rearrangements using [[Fluorescence in situ hybridization]] or to test for the fused ''FDGFRB-ATV6'' fluorescence in situ hybridization and/or [[Real-time polymerase chain reaction]] using appropriate nucleotide probes.<ref name="pmid26276769"/> These patients, unlike many patients with similarly appearing neoplasms, respond well to the tyrosine kinase inhibitor, [[imatinib]]. The drug often causes long-term complete hematological and cytogenic remissions as doses well below those used to treat [[chronic myelogenous leukemia#Treatment|chronic myelogenous leukemia]]. Primary or acquired [[drug resistance]] to this drug is very rare. Additional adjuvant [[chemotherapy]] may be necessary if a patient's disease is unresponsive to tyrosine kinase inhibitor therapy and/or progresses to more aggressive disease phase similar to that seen in the [[Chronic myelogenous leukemia#Blast crisis|blast crisis]] of chronic myelogenous leukemia.<ref name="pmid26276769"/><ref name="pmid28028030"/>
===== Other ''PDGFRB'' translocations =====
The ''PDGFRB'' gene has been found to fuse with at least 36 other genes to form fusion genes that encode chimeric proteins that are known or presumed to possess: '''a)''' continuously active PDGFRB-derived tyrosine kinase activity; '''b)''' the ability to continuously stimulate the growth and proliferation of hematological stem cells; and '''c)''' the ability to cause myeloid and lymphoid neoplasms that commonly but not always are associated with eosinophilia. In all instances, these gene fusion diseases are considered types of [[clonal eosinophilia]] with recommended treatment regimens very different than those of similar hematological malignancies. The genes fusing to ''PDGFRB'', their chromosomal location, and the notations describing their fused genes are given in the following table.<ref name="pmid28028030"/><ref name="pmid26276769"/>
{| class="wikitable"
|-
! Gene !! locus !! notation !! !! gene !! locus !! notation !!  !! Gene !! locus !! notation !! !! gene !! locus !! notation !! !! gene !! locus !! notation !! !! gene !! locus !! notation
|-
| ''[[TPM3]]'' || 1q21 || t(1;5)(q21;q32)|| || ''[[PDE4DIP]]'' || 1q22 || t(1;5)(q22;q32) || || ''[[SPTBN1]]'' || 2p16 || t(2;5)(p16;q32) || || ''[[GOLGA4]]'' || 3p21-25 || t(3;5)(p21-25;q31-35) || || ''WRD48''<ref name="ReferenceA">{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/57599 | title=WDR48 WD repeat domain 48 &#91;Homo sapiens (human)&#93; - Gene - NCBI}}</ref> || 3p21-22 || t(1;3;5)(p36;p21;q32) || || ''[[cGMP-dependent protein kinase|PRKG2]]''<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/5593 | title=PRKG2 protein kinase cGMP-dependent 2 &#91;Homo sapiens (human)&#93; - Gene - NCBI}}</ref>|| 4q21 || t(4;5)(p21;q32)
|-
| ''CEP85L''<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/387119 | title=CEP85L centrosomal protein 85 like &#91;Homo sapiens (human)&#93; - Gene - NCBI}}</ref> || 6q22 || t(5;6)(q32;q22) || || ''[[HIP1]]'' || 7q11 || t(5;7)(q32;q11) || || ''[[ANKRD15|KANK1]]'' || 9q24 || t(5;9)(q32;q24) || || ''[[BCR (gene)|BCR]]'' || 9q34 || t(5;9)(q32;q34) || || ''[[CCDC6]]'' || 10q21 || t(5;10)(q32;q21 || || ''H4(D10S170)''<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/?term=H4(D10S170) | title=CCDC6 coiled-coil domain containing 6 &#91;Homo sapiens (human)&#93; - Gene - NCBI}}</ref> || 10q21.2 || t(5;10)(q32;q21.2)
|-
| ''[[Caprin-1|GPIAP1]]''<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/4076 | title=CAPRIN1 cell cycle associated protein 1 &#91;Homo sapiens (human)&#93; - Gene - NCBI}}</ref> || 11p13 || multiple || || ''[[ETV6]]'' || 12p13 || t(5;12)q32;p13) || || ''[[ERC1]]'' || 12p13.3 || t(5;12)(q32;p13.3) || || ''[[GIT2]]'' || 12q24 || t(5;12)(q31-33;q24) || || ''NIN''<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/51199 | title=NIN ninein &#91;Homo sapiens (human)&#93; - Gene - NCBI}}</ref> || 14q24 || t(5;14)(q32;q24 || || ''[[TRIP11]]'' || 14q32 || t(5;14)(q32;q32)
|-
| ''CCDC88C''<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/440193 | title=CCDC88C coiled-coil domain containing 88C &#91;Homo sapiens (human)&#93; - Gene - NCBI}}</ref> || 14q32 || t(5;14)(q33;q32) || || ''[[TP53BP1]]'' || 15q22 || t(5;15)q33;22) || || ''[[NDE1]]'' || 16p13 || t(5;16)(q33;p13) || || ''[[SPECC1]]'' || 17p11 || t(5;17)(q32;p11.2) || || ''[[NDEL1]]'' || 17p13 || t(5;17)(q32;p13) || || ''[[MYO18A]]'' || 17q11.2 || t(5;17)(q32;q11.2)
|-
| ''BIN2''<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/51411 | title=BIN2 bridging integrator 2 &#91;Homo sapiens (human)&#93; - Gene - NCBI}}</ref> || 12q13 || t(5;12)(q32;q13) || || ''[[COL1A1]]'' || 17q22 || t(5;17)q32;q22) || || ''DTD1''<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/92675 | title=DTD1 D-tyrosyl-tRNA deacylase 1 &#91;Homo sapiens (human)&#93; - Gene - NCBI}}</ref> || 20p11 || t(5;20)(q32;p11) || || ''[[CPSF6]]'' || 12q15 || t(5;12)(q32;q15) || || ''[[RABEP1]]'' || 17p13 || t(5;17)(q32;p13) || || ''[[M-RIP|MPRIP]]'' || 17p11 || t(5;17)(q32;p11)
|-
| ''[[SPTBN1]]'' || 2p16 || t(5;2)(q32;p16) || || ''WDR48''<ref name="ReferenceA"/> || 3p22 || t(5;3)q32;p22) || || ''[[Giantin|GOLGB1]]'' || 3q12 || t(3;5)(q12;q32) || || ''[[DIAPH1]]'' || 5q31 || t(5;5)(q32;q31) || || ''[[TNIP1]]'' || 5q33 || t(5;5)(q32;q33) || || ''[[SART3]]'' || 12q23 || t(5;12)(q32;q23)
|-
|}
Similar to ''PDGFRB-ETV6'' translocations, these translocations are generally [[mutation#By impact on protein sequence|in-frame]] and encode for fusion proteins with their PDGFRB-derived tyrosine kinase being continuously active and responsible for causing the potentially malignant growth of its myeloid and/or lymphoid harboring cells. Patients are usually middle-aged men. They commonly present with anemia, eosinophilia, monocytosis, and splenomegaly and have their disease classified as chronic myelomonocytic leukemia, atypical chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, myelodysplastic syndrome, acute myelogenous leukemia, acute lymphoblastic leukemia, or [[Precursor T-lymphoblastic lymphoma|T lymphoblastic lymphoma]]. Diagnosis relies on cytogenetic analyses to detect breakpoints in the long arm of chromosome 5 by [[Fluorescence in situ hybridization]]. These patients usually respond well to [[imatinib]] therapy.<ref name="pmid28028030"/><ref name="pmid26276769"/><ref name="pmid26486351">{{cite journal | vauthors = Gotlib J | title = World Health Organization-defined eosinophilic disorders: 2015 update on diagnosis, risk stratification, and management | journal = American Journal of Hematology | volume = 90 | issue = 11 | pages = 1077–89 | year = 2015 | pmid = 26486351 | doi = 10.1002/ajh.24196 | s2cid = 42668440 | doi-access = free }}</ref>
===== Primary familial brain calcification =====
Primary familial brain calcification (see [[Fahr's syndrome]]) is a rare disease involving bilateral calcifications in the brain, predominantly in basal ganglia but also cerebellum, thalamus, and brainstem in patients presenting with diverse neurologic (e.g. movement disorders, parkinsonism, seizures, headache) features and psychiatric (e.g. cognitive impairment, mood disorders, psychotic symptoms, and obsessive-compulsive) disturbances. In a minority of cases, the disease is associated with apparent [[autosomal dominant]] loss of function mutations in ''PDGFRB'' or the gene which encodes a ligand that simulates PDGFRB, [[Platelet-derived growth factor]], ''PDGFB''. PDGFRB is extensively expressed in the neurons, chorioid plexus, vascular smooth muscle cells, and pericytes of the human brain, particularly the basal ganglia and the dentate nucleus. It is proposed that signal transduction through PDGFRB maintains blood–brain barrier integrity and that loss of the PDGFRB receptor or its ligand, PDGFB, disrupts  the blood–brain barrier, subsequently promoting (peri)vascular calcium deposition and thereby causing the dysfunction and death of neurons.<ref name="pmid25686319">{{cite journal | vauthors = Tadic V, Westenberger A, Domingo A, Alvarez-Fischer D, Klein C, Kasten M | title = Primary familial brain calcification with known gene mutations: a systematic review and challenges of phenotypic characterization | journal = JAMA Neurology | volume = 72 | issue = 4 | pages = 460–7 | year = 2015 | pmid = 25686319 | doi = 10.1001/jamaneurol.2014.3889 }}</ref><ref name="pmid28162874">{{cite journal | vauthors = Batla A, Tai XY, Schottlaender L, Erro R, Balint B, Bhatia KP | title = Deconstructing Fahr's disease/syndrome of brain calcification in the era of new genes | journal = Parkinsonism & Related Disorders | volume = 37 | pages = 1–10 | year = 2017 | pmid = 28162874 | doi = 10.1016/j.parkreldis.2016.12.024 | url = http://discovery.ucl.ac.uk/10045094/1/Revision%20clean%20updated7_11.pdf| type = Submitted manuscript }}</ref>
== Interactions ==
PDGFRB has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[CRK (gene)|CRK]],<ref name = pmid10733900>{{cite journal | vauthors = Matsumoto T, Yokote K, Take A, Takemoto M, Asaumi S, Hashimoto Y, Matsuda M, Saito Y, Mori S | title = Differential interaction of CrkII adaptor protein with platelet-derived growth factor alpha- and beta-receptors is determined by its internal tyrosine phosphorylation | journal = Biochem. Biophys. Res. Commun. | volume = 270 | issue = 1 | pages = 28–33 | date = April 2000 | pmid = 10733900 | doi = 10.1006/bbrc.2000.2374 }}</ref>
* [[Caveolin 1]],<ref name = pmid10066366>{{cite journal | vauthors = Yamamoto M, Toya Y, Jensen RA, Ishikawa Y | title = Caveolin is an inhibitor of platelet-derived growth factor receptor signaling | journal = Exp. Cell Res. | volume = 247 | issue = 2 | pages = 380–8 | date = March 1999 | pmid = 10066366 | doi = 10.1006/excr.1998.4379 }}</ref>
* [[Grb2]],<ref name = pmid10026169/><ref name = pmid7935391>{{cite journal | vauthors = Arvidsson AK, Rupp E, Nånberg E, Downward J, Rönnstrand L, Wennström S, Schlessinger J, Heldin CH, Claesson-Welsh L | title = Tyr-716 in the platelet-derived growth factor beta-receptor kinase insert is involved in GRB2 binding and Ras activation | journal = Mol. Cell. Biol. | volume = 14 | issue = 10 | pages = 6715–26 | date = October 1994 | pmid = 7935391 | pmc = 359202 | doi =  10.1128/mcb.14.10.6715}}</ref><ref name = pmid9362449>{{cite journal | vauthors = Tang J, Feng GS, Li W | title = Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth factor | journal = Oncogene | volume = 15 | issue = 15 | pages = 1823–32 | date = October 1997 | pmid = 9362449 | doi = 10.1038/sj.onc.1201351 | doi-access = free }}</ref>
* [[NCK1]],<ref name = pmid10026169>{{cite journal | vauthors = Braverman LE, Quilliam LA | title = Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck | journal = J. Biol. Chem. | volume = 274 | issue = 9 | pages = 5542–9 | date = February 1999 | pmid = 10026169 | doi =  10.1074/jbc.274.9.5542| doi-access = free }}</ref><ref name = pmid1333047>{{cite journal | vauthors = Li W, Hu P, Skolnik EY, Ullrich A, Schlessinger J | title = The SH2 and SH3 domain-containing Nck protein is oncogenic and a common target for phosphorylation by different surface receptors | journal = Mol. Cell. Biol. | volume = 12 | issue = 12 | pages = 5824–33 | date = December 1992 | pmid = 1333047 | pmc = 360522 | doi =  10.1128/MCB.12.12.5824}}</ref>
* [[NCK2]],<ref name = pmid10026169/><ref name = pmid9737977>{{cite journal | vauthors = Chen M, She H, Davis EM, Spicer CM, Kim L, Ren R, Le Beau MM, Li W | title = Identification of Nck family genes, chromosomal localization, expression, and signaling specificity | journal = J. Biol. Chem. | volume = 273 | issue = 39 | pages = 25171–8 | date = September 1998 | pmid = 9737977 | doi =  10.1074/jbc.273.39.25171| doi-access = free }}</ref><ref name = pmid11027258>{{cite journal | vauthors = Chen M, She H, Kim A, Woodley DT, Li W | title = Nckbeta adapter regulates actin polymerization in NIH 3T3 fibroblasts in response to platelet-derived growth factor bb | journal = Mol. Cell. Biol. | volume = 20 | issue = 21 | pages = 7867–80 | date = November 2000 | pmid = 11027258 | pmc = 86398 | doi =  10.1128/mcb.20.21.7867-7880.2000}}</ref>
* [[PDGFR-α]],<ref name = pmid7523122>{{cite journal | vauthors = Rupp E, Siegbahn A, Rönnstrand L, Wernstedt C, Claesson-Welsh L, Heldin CH | title = A unique autophosphorylation site in the platelet-derived growth factor alpha receptor from a heterodimeric receptor complex | journal = Eur. J. Biochem. | volume = 225 | issue = 1 | pages = 29–41 | date = October 1994 | pmid = 7523122 | doi =  10.1111/j.1432-1033.1994.00029.x| doi-access = free }}</ref><ref name = pmid2542288>{{cite journal | vauthors = Seifert RA, Hart CE, Phillips PE, Forstrom JW, Ross R, Murray MJ, Bowen-Pope DF | title = Two different subunits associate to create isoform-specific platelet-derived growth factor receptors | journal = J. Biol. Chem. | volume = 264 | issue = 15 | pages = 8771–8 | date = May 1989 | doi = 10.1016/S0021-9258(18)81860-9 | pmid = 2542288 | doi-access = free }}</ref>
* [[PTPN11]],<ref name = pmid11266449>{{cite journal | vauthors = Keilhack H, Müller M, Böhmer SA, Frank C, Weidner KM, Birchmeier W, Ligensa T, Berndt A, Kosmehl H, Günther B, Müller T, Birchmeier C, Böhmer FD | title = Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1 | journal = J. Cell Biol. | volume = 152 | issue = 2 | pages = 325–34 | date = January 2001 | pmid = 11266449 | pmc = 2199605 | doi =  10.1083/jcb.152.2.325}}</ref><ref name = pmid7691811>{{cite journal | vauthors = Lechleider RJ, Sugimoto S, Bennett AM, Kashishian AS, Cooper JA, Shoelson SE, Walsh CT, Neel BG | title = Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor | journal = J. Biol. Chem. | volume = 268 | issue = 29 | pages = 21478–81 | date = October 1993 | doi = 10.1016/S0021-9258(20)80562-6 | pmid = 7691811 | doi-access = free }}</ref>
* [[RAS p21 protein activator 1]],<ref name = pmid10697503>{{cite journal | vauthors = Farooqui T, Kelley T, Coggeshall KM, Rampersaud AA, Yates AJ | title = GM1 inhibits early signaling events mediated by PDGF receptor in cultured human glioma cells | journal = Anticancer Res. | volume = 19 | issue = 6B | pages = 5007–13 | pmid = 10697503 | year=1999}}</ref><ref name = pmid11896619>{{cite journal | vauthors = Ekman S, Kallin A, Engström U, Heldin CH, Rönnstrand L | title = SHP-2 is involved in heterodimer specific loss of phosphorylation of Tyr771 in the PDGF beta-receptor | journal = Oncogene | volume = 21 | issue = 12 | pages = 1870–5 | date = March 2002 | pmid = 11896619 | doi = 10.1038/sj.onc.1205210 | doi-access = free }}</ref>
* [[SHC1]]<ref name = pmid8195171>{{cite journal | vauthors = Yokote K, Mori S, Hansen K, McGlade J, Pawson T, Heldin CH, Claesson-Welsh L | title = Direct interaction between Shc and the platelet-derived growth factor beta-receptor | journal = J. Biol. Chem. | volume = 269 | issue = 21 | pages = 15337–43 | date = May 1994 | doi = 10.1016/S0021-9258(17)36611-5 | pmid = 8195171 | doi-access = free }}</ref>  and
* [[Sodium-hydrogen antiporter 3 regulator 1]].<ref name = pmid11046132>{{cite journal | vauthors = Maudsley S, Zamah AM, Rahman N, Blitzer JT, Luttrell LM, Lefkowitz RJ, Hall RA | title = Platelet-derived growth factor receptor association with Na(+)/H(+) exchanger regulatory factor potentiates receptor activity | journal = Mol. Cell. Biol. | volume = 20 | issue = 22 | pages = 8352–63 | date = November 2000 | pmid = 11046132 | pmc = 102142 | doi =  10.1128/mcb.20.22.8352-8363.2000}}</ref>
{{Div col end}}
==Notes==
{{Academic-written review|Q=Q39166181}}
== See also ==
* [[Cluster of differentiation]]
* [[Platelet-derived growth factor receptor]]
* [[Kosaki overgrowth syndrome]]
== References ==
{{reflist|33em}}
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Hart CE, Bowen-Pope DF | title = Platelet-derived growth factor receptor: current views of the two-subunit model | journal = J. Invest. Dermatol. | volume = 94 | issue = 6 Suppl | pages = 53S–57S | year = 1990 | pmid = 2161888 | doi = 10.1111/1523-1747.ep12875065 | doi-access = free }}
* {{cite journal | vauthors = Steer EJ, Cross NC | title = Myeloproliferative disorders with translocations of chromosome 5q31-35: role of the platelet-derived growth factor receptor Beta | journal = Acta Haematol. | volume = 107 | issue = 2 | pages = 113–22 | year = 2002 | pmid = 11919393 | doi = 10.1159/000046641 | s2cid = 202646911 }}
{{refend}}
== External links ==
* {{MeshName|CD140B+Antigen}}
{{Clusters of differentiation}}
{{Growth factor receptors}}
{{Tyrosine kinases}}
{{Enzymes}}
{{Growth factor receptor modulators}}
{{Portal bar|Biology|border=no}}
[[Category:Clusters of differentiation]]
[[Category:Genes on human chromosome 12]]
[[Category:Tyrosine kinase receptors]]