platelet-derived growth factor receptor

• 血小板由来増殖因子受容体、血小板由来増殖因子レセプター、血小板由来成長因子受容体、血小板由来成長因子レセプター

関

PDGF receptor

WordNet

1. cultivate by growing, often involving improvements by means of agricultural techniques; "The Bordeaux region produces great red wines"; "They produce good ham in Parma"; "We grow wheat here"; "We raise hogs here" (同)raise, farm, produce
2. come to have or undergo a change of (physical features and attributes); "He grew a beard"; "The patient developed abdominal pains"; "I got funny spots all over my body"; "Well-developed breasts" (同)develop, produce, get, acquire
3. become attached by or as if by the process of growth; "The tree trunks had grown together"
4. become larger, greater, or bigger; expand or gain; "The problem grew too large for me"; "Her business grew fast"
5. cause to grow or develop; "He grows vegetables in his backyard"
6. increase in size by natural process; "Corn doesnt grow here"; "In these forests, mushrooms grow under the trees"; "her hair doesnt grow much anymore"
7. (biology) the process of an individual organism growing organically; a purely biological unfolding of events involved in an organism changing gradually from a simple to a more complex level; "he proposed an indicator of osseous development in children" (同)growing, maturation, development, ontogeny, ontogenesis
8. (pathology) an abnormal proliferation of tissue (as in a tumor)
9. a progression from simpler to more complex forms; "the growth of culture"
10. something grown or growing; "a growth of hair"
11. vegetation that has grown; "a growth of trees"; "the only growth was some salt grass"
12. be a contributing factor; "make things factor into a companys profitability"
13. any of the numbers (or symbols) that form a product when multiplied together
14. an independent variable in statistics
15. anything that contributes causally to a result; "a number of factors determined the outcome"
16. consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
17. resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
18. an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
19. a concept whose truth can be proved; "scientific hypotheses are not facts"
20. a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
21. a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
22. obtain; "derive pleasure from ones garden" (同)gain
23. develop or evolve from a latent or potential state (同)educe
24. come from; "The present name derives from an older form"
25. come from; be connected by a relationship of blood, for example; "She was descended from an old Italian noble family"; "he comes from humble origins" (同)come, descend

PrepTutorEJDIC

1. 『成長する』,育つ,〈植物が〉生える,茂る / (類・量・程などにおいて)『増大する』,大きくなる / 『しだいになる』 / …‘を'成長させる,大きくする,育てる / …から生じる(起こる)
2. 〈U〉(…の)『成長』,発育;『発達』,発展《+『of』+『名』》 / 〈U〉(数・量,重要性・力などの)『増加』,増大,拡張《+『of』+『名』》 / 〈U〉《修飾語[句]を伴って》栽培,生産,…産 / 〈C〉成育した物,(草,木,髪,ひげなどの)生えたもの / 〈C〉腫瘍(しゅよう)
3. (…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
4. 〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
5. 《『derive』+『名』+『from』+『名』(do『ing』)》(…から)…‘を'『引き出す』,得る,求める / 《『derive from』+『名』(do『ing』)》《文》(…から)派生する,(…に)由来する

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/09/02 09:13:48」(JST)

wiki en

[Wiki en表示]

platelet-derived growth factor receptor, alpha polypeptide
Identifiers
Symbol	PDGFRA
Entrez	5156
HUGO	8803
OMIM	173490
RefSeq	NM_006206
UniProt	P16234
Other data
Locus	Chr. 4 q12

platelet-derived growth factor receptor, beta polypeptide
Ribbon image of two molecules of human PDGF receptor beta (yellow and magenta) in complex with dimeric PDGF-B (cyan and green).
Identifiers
Symbol	PDGFRB
Alt. symbols	PDGFR
Entrez	5159
HUGO	8804
OMIM	173410
RefSeq	NM_002609
UniProt	P09619
Other data
Locus	Chr. 5 q31-q32

Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including cancer. There are two forms of the PDGF-R, alpha and beta each encoded by a different gene. Depending on which growth factor is bound, PDGF-R homo- or heterodimerizes.

Mechanism of action

The PDGF family consists of PDGF-A, -B, -C and -D, which form either homo- or heterodimers (PDGF-AA, -AB, -BB, -CC, -DD). The four PDGFs are inactive in their monomeric forms. The PDGFs bind to the protein tyrosine kinase receptors PDGF receptor-α and -β. These two receptor isoforms dimerize upon binding the PDGF dimer, leading to three possible receptor combinations, namely -αα, -ββ and -αβ. The extracellular region of the receptor consists of five immunoglobulin-like domains while the intracellular part is a tyrosine kinase domain. The ligand-binding sites of the receptors are located to the three first immunoglobulin-like domains. PDGF-CC specifically interacts with PDGFR-αα and -αβ, but not with -ββ, and thereby resembles PDGF-AB. PDGF-DD binds to PDGFR-ββ with high affinity, and to PDGFR-αβ to a markedly lower extent and is therefore regarded as PDGFR-ββ specific. PDGF-AA binds only to PDGFR-αα, while PDGF-BB is the only PDGF that can bind all three receptor combinations with high affinity.

Dimerization is a prerequisite for the activation of the kinase. Kinase activation is visualized as tyrosine phosphorylation of the receptor molecules, which occurs between the dimerized receptor molecules (transphosphorylation). In conjunction with dimerization and kinase activation, the receptor molecules undergo conformational changes, which allow a basal kinase activity to phosphorylate a critical tyrosine residue, thereby "unlocking" the kinase, leading to full enzymatic activity directed toward other tyrosine residues in the receptor molecules as well as other substrates for the kinase. Expression of both receptors and each of the four PDGFs is under independent control, giving the PDGF/PDGFR system a high flexibility. Different cell types vary greatly in the ratio of PDGF isoforms and PDGFRs expressed. Different external stimuli such as inflammation, embryonic development or differentiation modulate cellular receptor expression allowing binding of some PDGFs but not others. Additionally, some cells display only one of the PDGFR isoforms while other cells express both isoforms, simultaneously or separately.

Interaction with signal transduction molecules

Tyrosine phosphorylation sites in growth factor receptors serve two major purposes: to control the state of activity of the kinase and to create binding sites for downstream signal transduction molecules, which in many cases also are substrates for the kinase. The second part of the tyrosine kinase domain in the PDGFβ receptor is phosphorylated at Tyr-857, and mutant receptors carrying phenylalanine at this position have reduced kinase activity. Tyr-857 has therefore been assigned a role in positive regulation of kinase activity. Sites of tyrosine phosphorylation involved in binding signal transduction molecules have been identified in the juxtamembrane domain, the kinase insert, and in the C-terminal tail in the PDGFβ receptor. The phosphorylated tyrosine residue and in general three adjacent C-terminal amino acid residues form specific binding sites for signal transduction molecules. Binding to these sites involves a common conserved stretches, denoted the Src homology (SH) 2 domain and/or Phosphotyrosine Binding Domains (PTB). The specificity of these interactions appears to be very high, since mutant receptors carrying phenylalanine residues in one or several of the different phosphorylation sites generally lack the capacity to bind the targeted signal transduction molecule. The signal transduction molecules are either equipped with different enzymatic activities, or they are adaptor molecules, which in some but not all cases are found in complexes with subunits that carry a catalytic activity. Upon interaction with the activated receptor, the catalytic activities become up-regulated, through tyrosine phosphorylation or other mechanisms, generating a signal that may be unique for each type of signal transduction molecule.

Examination of the different signalling cascades, induced by RTKs, established Ras/mitogen-activated protein kinase (MAPK),PI-3 kinase and phospholipase-γ (PLCγ) pathways as key downstream mediators of the PDGFR signalling. In addition, reactive oxygen species (ROS)-dependent STAT3 activation has been established to be a key downstream mediator of PDGFR signalling in vascular smooth muscle cells.

MAPK pathway

The adaptor protein Grb2 forms a complex with Sos by the Grb2 SH3 domain. Grb2 (or) the Grb2/Sos complex is recruited to the membrane by the Grb2 SH2 domain binding to activated PDGFR-bound SHP2 (Also known as PTPN11, a cytosolic PTP), thereby allowing interaction with Ras and the exchange of GDP for GTP on Ras. Whereas the interaction between Grb2 and PDGFR occurs through interaction with the SHP2 protein, Grb2 binds to activated EGFR through Shc, another adaptor protein that forms a complex with many receptors via its PTB domain. Once activated, Ras interacts with several proteins, namely Raf. Activated Raf stimulates MAPK-kinase (MAPKK or MEK) by phosphorylating a Ser residue in its activation loop. MAPKK then phosphorylates MAPK (ERK1/2) on T and Y residues at the activation-loop leading to its activation. Activated MAPK phosphorylates a variety of cytoplasmic substrates, as well as transcription factors, when translocated into the nucleus. MAPK family members have been found to regulate various biological functions by phosphorylation of particular target molecules (such as transcription factors, other kinases etc.) located in cell membrane, cytoplasm and nucleus, and thus contribute to the regulation of different cellular processes such as cell proliferation, differentiation, apoptosis and immunoresponses.

PI3K pathway

The class IA phospholipid kinase, PI-3 kinase, is activated by the majority of RTKs. Similarly to other SH2 domain-containing proteins, PI-3 kinase forms a complex with PY sites on activated receptors. The main function of PI3K activation is the generation of PIP3, which functions as a second messenger to activate downstream tyrosine kinases Btk and Itk, the Ser/Thr kinases PDK1 and Akt (PKB). The major biological functions of Akt activation can be classified into three categories – survival,proliferation and cell growth. Akt is also known to be implicated in several cancers, particularly breast. PLCγ is immediately recruited by an activated RTK through the binding of its SH2 domains to phosphotyrosine sites of the receptor. After activation, PLCγ hydrolyses its substrate PtdIns(4,5)P2 and forms two second messengers, diacylglycerol and Ins(1,4,5)P3. Ins(1,4,5)P3 stimulates the release of Ca 2+ from intracellular supplies. Ca 2+ then binds to calmodulin, which subsequently activates a family of calmodulindependent protein kinases (CamKs). In addition, both diacylglycerol and Ca 2+ activate members of the PKC family. The second messengers generated by PtdIns(4,5)P2 hydrolysis stimulate a variety of intracellular processes such as proliferation,angiogenesis, cell motility.

See also

• Receptor tyrosine kinase
• PDGF
• Imatinib
• PDGFRA
• PDGFRB
• Crenolanib (CP-868,596-26)

References

External links

• Platelet-Derived Growth Factor Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)

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Related Links

• Activation of platelet-derived growth factor receptor alpha ...

1. PLoS One. 2014 Mar 25;9(3):e92925. doi: 10.1371/journal.pone.0092925. eCollection 2014. Activation of platelet-derived growth factor receptor alpha contributes to liver fibrosis. Hayes BJ(1), Riehle KJ(2), Shimizu ...

• PDGFRL - platelet-derived growth factor receptor-like ...

The official name of this gene is “platelet-derived growth factor receptor-like.” PDGFRL is the gene's official symbol. The PDGFRL gene is also known by other names, listed below. Read more about gene names and ...

Related Pictures

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★リンクテーブル★

リンク元	「血小板由来成長因子受容体」「血小板由来成長因子レセプター」「血小板由来増殖因子レセプター」「PDGF receptor」
関連記事	「derive」「grow」「fact」「factor」「growth」

「血小板由来成長因子受容体」

　　[★]

英

platelet-derived growth factor receptor、PDGF receptor

関

PDGF受容体、血小板由来成長因子レセプター、PDGFレセプター、血小板由来増殖因子レセプター、血小板由来増殖因子受容体

• 同受容体のチロシンキナーゼがイマチニブの標的となる。

• BCR-ALB/C-KIT/PDGFR阻害薬

• イマチニブ imatinib
• dasatinib, nilotinib

「血小板由来成長因子レセプター」

　　[★]

英

platelet-derived growth factor receptor、PDGF receptor

関

PDGF受容体、PDGFレセプター、血小板由来成長因子受容体、血小板由来増殖因子レセプター、血小板由来増殖因子受容体

「血小板由来増殖因子レセプター」

　　[★]

英

platelet-derived growth factor receptor

関

PDGF受容体、血小板由来成長因子レセプター、血小板由来成長因子受容体、血小板由来増殖因子受容体

「PDGF receptor」

　　[★]

• 血小板由来成長因子受容体、血小板由来成長因子レセプター、PDGF受容体、PDGFレセプター

関

platelet-derived growth factor receptor

「derive」

　　[★]

• vt.

• 由来する

同

stem

• 由来する、派生する、引き出す

関

borne、come from、descend、draw、educe、elicit、stem

　 　 　 　 　

「grow」

　　[★]

• v.

(過去: grew-過去分詞: grown)

• 成長する、生育する、伸びる

関

extend、growth、outgrow、outgrowth、stretch

　 　 　 　 　 　 　

「fact」

　　[★]

• n.

• 事実、現状、実際、実態

関

actual、actually、in fact、in practice、indeed、practically

　 　 　 　 　

「factor」

　　[★]

• n.

• 因子、要因、要素、ファクター

関

element、elementary、factorial、parameter

　 　 　 　 　 　 　

「growth」

　　[★]

• n.

• 成長