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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2020/05/10 11:22:38」(JST)

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PDGF B, Human.

血小板由来成長因子（けっしょうばんゆらいせいちょういんし、英:Platelet-Derived Growth Factor、PDGF）とは主に間葉系細胞（線維芽細胞、平滑筋細胞、グリア細胞等）の遊走および増殖などの調節に関与する増殖因子であり、PDGF/VEGFファミリーに属する。主に巨核球によって産生されるほか、血小板のα顆粒中にも含まれる。後の研究により、PDGFは上皮細胞や内皮細胞など様々な細胞によって産生されることが分かっている。PDGFにはPDGF-A、B、CおよびDの少なくとも4種類が存在するが、A鎖およびB鎖はジスルフィド結合を形成することによりホモあるいはヘテロ2量体構造をとり3種類のアイソフォーム（PDGF-AA、AB、BB）を有している。PDGFはチロシンキナーゼ関連型であるPDGF受容体（PDGFR）を介してその生理作用を発現することが知られている。

発見の経緯

アレクシス・カレル(1873-1944)。

20世紀初頭、アレクシス・カレル（Alexis Carrel）は生理食塩水中において組織を培養しようとすると細胞がやがて死滅することに疑問を抱き、研究を行った。彼はこの生理食塩水に対して血漿を補充したり細胞を血清に浸すことによって細胞の増殖維持が可能となることを発見したが血清中にある成分が細胞増殖活性を持つという考えにまでは至らなかった。その後、ハワード・テミン（Howard Temin）及びレナート・ドゥルベッコ(Renato Dulbecco)がそれぞれ独立して細胞の増殖に関与する成分が血清中に存在することを見出した。血漿と異なり、血清中には血小板に由来する物質が含まれているためこれが血清のより大きな細胞増殖活性をもたらしている可能性が考えられた。1974年にこの血清中の物質が血管平滑筋の増殖を促す作用を持つことが分かり、血小板由来成長因子と名付けられた。1979年にはPDGFが精製され、その構造も明らかになった。PGDF-Bはサル肉腫ウイルスの癌遺伝子v-sisと92%の相同性を有することが明らかになっており^[1]、現在では発癌への関与が注目されている。また、2000年にはPDGF-C^[2]が、2001年にはPDGF-D^[3]がそれぞれ発見されている。

遺伝子および分子構造

遺伝子	遺伝子座	アミノ酸残基数	PDGF/VEGFドメイン	CUBドメイン	ノックアウトマウスの表現系
PDGFA	7p22	196 または 211	O	X	胎生期10日以前あるいは生後早期に死亡^[4]
PDGFB	22q13	241	O	X	胎生期後期に致死（腎の未成熟や血管系の異常形成による^[5]^[6]）
PDGFC	4q31	345	O	O	－
PDGFD	11q22	370	O	O	－

PDGF-AおよびBは8つのよく保存されたシステイン残基を有しており、これらの残基同士で分子内ジスルフィド結合（R-S-S-R'）を形成している。カルボキシル基（-CO₂H）側にはPDGF/VEGFドメインが存在し、アミノ基（-NH₂）側に存在するCUBドメインはPDGF-CおよびPDGF-Dに見られる。CUBドメインはおよそ110個のアミノ酸から構成される。PDGF-AおよびBはアミノ基側のプロドメインを切断されることにより活性化を受けてから分泌される性質をもつ。両者（A、B）の成熟体の間においては互いに60%の相同性を有している。PDGFA遺伝子の転写機構には6番目のエキソンにおける選択的スプライシングが存在し、細胞内においては一般に短型が多い。PDGF-CおよびDは分泌されたのちにアミノ基側のCUBドメインの切断除去を受けて他のアイソフォームと同様にホモ二量体を形成するが、ヘテロ二量体を形成しうるかについてはよく分かっていない。

受容体

PDGFRβの構造。

チロシンキナーゼ関連型受容体の一種であるPDGFRには構造的に類似した2種類のサブタイプが存在し、それぞれPDGFRαおよびβと呼ばれており、ヒトの染色体では4q11-12、5q31-32に位置する。PDGFRAおよびPDGFRB遺伝子は互いに構造が類似しており、それぞれ約69kb、約43kbの長さを持ち、23個のエキソンを有する。PDGFRA遺伝子は幹細胞増殖因子（SCF）受容体であるc-kitをコードする遺伝子と、PDGFRB遺伝子はCSF-1受容体の遺伝子と位置・構造が近く、同一の遺伝子から進化したと考えられている。いずれのサブタイプも5つの免疫グロブリン様ドメイン細胞外に有し、さらに1つの細胞膜貫通ドメインと細胞内にはエフェクター分子やアダプター分子の結合に必要なドメインを有している。通常これらの受容体タンパク質は細胞膜上に単量体で存在しているがリガンドの結合によってPDGFRをはじめとしたチロシンキナーゼ関連型受容体は二量体を形成することが知られており、PDGFR-αα、PDGFR-αβ、PDGFR-ββの三種類の組み合わせが存在する。これらの複合体はそれぞれリガンドに対する親和性が異なり、各PDGF二量体がどの受容体を活性化しうるかについて以下に示した。

	PDGF-AA	PDGF-AB	PDGF-BB	PDGF-CC	PDGF-DD
PDGFR-αα	O	O	O	O	X
PDGFR-αβ	X	O	O	O	?
PDGFR-ββ	X	X	O	O	O

リガンドとの結合によりPDGFRのチロシン残基が自己リン酸化を受け、SH2ドメインを有するシグナル伝達分子（PLC-γ、Grb2、PI3Kなど）との結合部位となり下流へシグナルを伝える。

生理作用

PDGFは細胞遊走や形質転換等を引き起こし、胎児の成長や血管新生にも関与していると考えられている。血管や線維芽細胞では炎症および創傷治癒の過程においてPDGFRβの発現が上昇することも報告されている^[7]^[8]。また、PDGFはある種の疾患の進行に関与しており、PDGFおよびPDGFRの過剰発現はアテローム性動脈硬化や線維増殖性疾患の発症と関連がある。さらに、PVDFは細胞周期をG1/S期において制御している。ニューロンやグリア細胞はPDGFおよびその受容体を発現しており、分化・増殖を促している^[9]^[10]。

出典

今堀和友、山川民夫編集『生化学辞典第4版』東京化学同人 2007年 ISBN 9784807906703
Gomperts BD, Kramer IM and Tatham PE 原著『シグナル伝達』メディカル・サイエンス・インターナショナル 2004年 ISBN 489592369X
宮園浩平、菅村和夫編『BioScience 用語ライブラリーサイトカイン･増殖因子』羊土社 1998年 ISBN 4897062616

参考文献

^ Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA and Antoniades HN.(1983)"Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor."Science. 221,275-7. PMID 6304883
^ Li X, Ponten A, Aase K, Karlsson L, Abramsson A, Uutela M, Backstrom G, Hellstrom M, Bostrom H, Li H, Soriano P, Betsholtz C, Heldin CH, Alitalo K, Ostman A and Eriksson U.(2000)"PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor."Nat.Cell.Biol. 2,302-9. PMID 10806482
^ LaRochelle WJ, Jeffers M, McDonald WF, Chillakuru RA, Giese NA, Lokker NA, Sullivan C, Boldog FL, Yang M, Vernet C, Burgess CE, Fernandes E, Deegler LL, Rittman B, Shimkets J, Shimkets RA, Rothberg JM and Lichenstein HS.(2001)"PDGF-D, a new protease-activated growth factor."Nat.Cell.Biol. 3,517-21. PMID 11331882
^ Boström H, Willetts K, Pekny M, Levéen P, Lindahl P, Hedstrand H, Pekna M, Hellström M, Gebre-Medhin S, Schalling M, Nilsson M, Kurland S, Törnell J, Heath JK and Betsholtz C.(1996)"PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis."Cell. 85,863-73. PMID 8681381
^ Levéen P, Pekny M, Gebre-Medhin S, Swolin B, Larsson E and Betsholtz C.(1994)"Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities."Genes Dev. 8,1875-87. PMID 7958863
^ Lindahl P, Johansson BR, Levéen P and Betsholtz C.(1997)"Pericyte loss and microaneurysm formation in PDGF-B-deficient mice."Science. 277,242-5. PMID 9211853
^ Reuterdahl C, Tingström A, Terracio L, Funa K, Heldin CH and Rubin K.(1991)"Characterization of platelet-derived growth factor beta-receptor expressing cells in the vasculature of human rheumatoid synovium."Lab.Invest. 64,321-9. PMID 1848332
^ Reuterdahl C, Sundberg C, Rubin K, Funa K and Gerdin B.(1993)"Tissue localization of beta receptors for platelet-derived growth factor and platelet-derived growth factor B chain during wound repair in humans."J.Clin.Invest. 91,2065-75. PMID 8486774
^ Eccleston PA, Funa K and Heldin CH.(1993)"Expression of platelet-derived growth factor (PDGF) and PDGF alpha- and beta-receptors in the peripheral nervous system: an analysis of sciatic nerve and dorsal root ganglia."Dev.Biol. 155,459-70. PMID 8432400
^ Erlandsson A, Enarsson M and Forsberg-Nilsson K.(2001)"Immature neurons from CNS stem cells proliferate in response to platelet-derived growth factor."J.Neurosci. 21,3483-91. PMID 11331377

wiki en

[Wiki en表示]

platelet-derived growth factor receptor, beta polypeptide
Identifiers
Symbol	PDGFRB
Alt. symbols	PDGFR
NCBI gene	5159
HGNC	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.^[2] There are two forms of the PDGF-R, alpha and beta each encoded by a different gene.^[3] Depending on which growth factor is bound, PDGF-R homo- or heterodimerizes.^[4]

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.^[5]

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.^[6] 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 signaling cascades induced by RTKs established Ras/mitogen-activated protein kinase (MAPK), PI-3 kinase, and phospholipase-γ (PLCγ) pathways as key downstream mediators of PDGFR signaling.^[7]^[8] In addition, reactive oxygen species (ROS)-dependent STAT3 activation has been established to be a key downstream mediator of PDGFR signaling in vascular smooth muscle cells.^[9]

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 instead binds to activated EGFR through Shc, another adaptor protein that forms a complex with many receptors via its PTB domain.^[10] Once activated, Ras interacts with several proteins, namely Raf. Activated Raf stimulates MAPK-kinase (MAPKK or MEK) by phosphorylating a serine 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.

References

^ PDB: 3MJG; Shim AH, Liu H, Focia PJ, Chen X, Lin PC, He X (June 2010). "Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex". Proceedings of the National Academy of Sciences of the United States of America. 107 (25): 11307–12. doi:10.1073/pnas.1000806107. PMC 2895058. PMID 20534510.; rendered using PyMOL.
^ Williams LT (March 1989). "Signal transduction by the platelet-derived growth factor receptor". Science. 243 (4898): 1564–70. doi:10.1126/science.2538922. PMID 2538922.
^ Heldin CH, Westermark B (April 1989). "Platelet-derived growth factor: three isoforms and two receptor types". Trends in Genetics. 5 (4): 108–11. doi:10.1016/0168-9525(89)90040-1. PMID 2543106.
^ Heldin CH, Ostman A, Eriksson A, Siegbahn A, Claesson-Welsh L, Westermark B (March 1992). "Platelet-derived growth factor: isoform-specific signalling via heterodimeric or homodimeric receptor complexes". Kidney International. 41 (3): 571–4. doi:10.1038/ki.1992.84. PMID 1315403.
^ Cao Y, Cao R, Hedlund EM (July 2008). "R Regulation of tumor angiogenesis and metastasis by FGF and PDGF signaling pathways". Journal of Molecular Medicine. 86 (7): 785–9. doi:10.1007/s00109-008-0337-z. PMID 18392794.
^ Kazlauskas A, Cooper JA (September 1989). "Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins". Cell. 58 (6): 1121–33. doi:10.1016/0092-8674(89)90510-2. PMID 2550144.
^ Valius M, Kazlauskas A (April 1993). "Phospholipase C-gamma 1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor's mitogenic signal". Cell. 73 (2): 321–34. doi:10.1016/0092-8674(93)90232-F. PMID 7682895.
^ Montmayeur JP, Valius M, Vandenheede J, Kazlauskas A (December 1997). "The platelet-derived growth factor beta receptor triggers multiple cytoplasmic signaling cascades that arrive at the nucleus as distinguishable inputs". The Journal of Biological Chemistry. 272 (51): 32670–8. doi:10.1074/jbc.272.51.32670. PMID 9405485.
^ Blazevic T, Schwaiberger AV, Schreiner CE, Schachner D, Schaible AM, Grojer CS, Atanasov AG, Werz O, Dirsch VM, Heiss EH (December 2013). "12/15-lipoxygenase contributes to platelet-derived growth factor-induced activation of signal transducer and activator of transcription 3". The Journal of Biological Chemistry. 288 (49): 35592–603. doi:10.1074/jbc.M113.489013. PMC 3853304. PMID 24165129.
^ Schlessinger, J. SH2/SH3 Signaling Proteins. Curr. Op. Gen. Dev. 1994, 4(1):25-30.

External links

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

UpToDate Contents

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「イマチニブ」

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

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Platelet-derived growth factor receptor
	Ribbon image of two molecules of human PDGF receptor beta (yellow and magenta) in complex with dimeric PDGF-B (cyan and green).
Identifiers
Symbol	PDGFR
Pfam	PF04692
InterPro	IPR006782
Membranome	1204
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

　　[★]

英: imatinib
化: imatinib mesylate
商: グリベック
関: nib; 分子標的薬剤

分類

その他

チロシンキナーゼ阻害薬

概念

低分子のチロシンキナーゼ阻害薬である。
最初はPDGFRに特異的な阻害薬である2-phenylaminopyrimidine誘導体として開発された。
t(9;22)の染色体転座を有する慢性骨髄性白血病でみられるBCR-ABL融合蛋白を含め、ABLキナーゼに対する強い阻害作用を持つことが明らかとなった。
また受容体チロシンキナーゼであるC-KITのキナーゼも阻害することが明らかとなった。
造血幹細胞因子(SCF)の受容体はC-KITであるが、C-KITの変異はGISTやsystemic mastocytosisでしばしば見られる。
FIPL1-PDGFRA融合蛋白質の発現が特徴的なidiopathic hypereosinophilic syndromeはイマチニブ投与によりPDGFRAで阻害することで治療が成功する。

特徴

構造

作用機序

ABLや、活性複合体であるv-ABL, BCR-ABL, [EVT6]-ABLを阻害する (GOO.1367)

(そのほかに)PDGFRとKITに対しても競合阻害作用を持つ (GOO.1367)

KITはgastrointestinal stromal tumor(GIST)と関連

ETV6-PDGFRはchronic myelomonocytic leukemia(CMML)と関連

FIP1L1-PDGFRAはhypereosinophilic syndrome(HES)と関連

薬理作用

動態

経口投与

適応

慢性骨髄性白血病 chronic myelocytic leukemia CML
胃腸間質性腫瘍 astrointestinal stromal tumors
好酸球増多症候群 hypereosinophilic syndrome

グリベック錠100mg

1. 慢性骨髄性白血病
2. KIT陽性消化管間質腫瘍
3. フィラデルフィア染色体陽性急性リンパ性白血病

注意

禁忌

副作用

表在性浮腫、嘔気・嘔吐、筋痙攣、皮疹、下痢

相互作用

類似薬

添付文書

グリベック錠100mg

http://www.info.pmda.go.jp/go/pack/4291011F1028_1_11/4291011F1028_1_11?view=body

「モテサニブ」

　　[★]

英: motesanib
開発名: AMG706

多キナーゼ阻害薬の一つ

多キナーゼ阻害薬には
スニチニブ sunitinib
ソラフェニブ sorafenib
ヴァラチニブ valatinib

オーロラ阻害薬　パゾパニブ pazopanibというのもあるらしい

作用機序
血管内皮増殖因子受容体 VEGFR1,2,3、血小板由来増殖因子受容体 PDGFR、SCF受容体 c-KITに結合することによる

文献

Efficacy and safety of motesanib, an oral inhibitor of VEGF, PDGF, and Kit receptors, in patients with imatinib-resistant gastrointestinal stromal tumors.

Cancer Chemother Pharmacol. 2010 Sep 14. [Epub ahead of print]

Benjamin RS, Schoffski P, Hartmann JT, Van Oosterom A, Bui BN, Duyster J, Schuetze S, Blay JY, Reichardt P, Rosen LS, Skubitz K, McCoy S, Sun YN, Stepan DE, Baker L.

PMID 20838998

参考

mikanbox

http://www.mikanbox.com/md-lab/column/imashuku/Column6/column6_25.html

「PDGF」

　　[★] 血小板由来成長因子

同: platelel-derived growth factor

同: platelet-derived growth factor

[1] Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA and Antoniades HN.(1983)"Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor."Science. 221,275-7. PMID 6304883

[2] Li X, Ponten A, Aase K, Karlsson L, Abramsson A, Uutela M, Backstrom G, Hellstrom M, Bostrom H, Li H, Soriano P, Betsholtz C, Heldin CH, Alitalo K, Ostman A and Eriksson U.(2000)"PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor."Nat.Cell.Biol. 2,302-9. PMID 10806482

[3] LaRochelle WJ, Jeffers M, McDonald WF, Chillakuru RA, Giese NA, Lokker NA, Sullivan C, Boldog FL, Yang M, Vernet C, Burgess CE, Fernandes E, Deegler LL, Rittman B, Shimkets J, Shimkets RA, Rothberg JM and Lichenstein HS.(2001)"PDGF-D, a new protease-activated growth factor."Nat.Cell.Biol. 3,517-21. PMID 11331882

[4] Boström H, Willetts K, Pekny M, Levéen P, Lindahl P, Hedstrand H, Pekna M, Hellström M, Gebre-Medhin S, Schalling M, Nilsson M, Kurland S, Törnell J, Heath JK and Betsholtz C.(1996)"PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis."Cell. 85,863-73. PMID 8681381

[5] Levéen P, Pekny M, Gebre-Medhin S, Swolin B, Larsson E and Betsholtz C.(1994)"Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities."Genes Dev. 8,1875-87. PMID 7958863

[6] Lindahl P, Johansson BR, Levéen P and Betsholtz C.(1997)"Pericyte loss and microaneurysm formation in PDGF-B-deficient mice."Science. 277,242-5. PMID 9211853

[7] Reuterdahl C, Tingström A, Terracio L, Funa K, Heldin CH and Rubin K.(1991)"Characterization of platelet-derived growth factor beta-receptor expressing cells in the vasculature of human rheumatoid synovium."Lab.Invest. 64,321-9. PMID 1848332

[8] Reuterdahl C, Sundberg C, Rubin K, Funa K and Gerdin B.(1993)"Tissue localization of beta receptors for platelet-derived growth factor and platelet-derived growth factor B chain during wound repair in humans."J.Clin.Invest. 91,2065-75. PMID 8486774

[9] Eccleston PA, Funa K and Heldin CH.(1993)"Expression of platelet-derived growth factor (PDGF) and PDGF alpha- and beta-receptors in the peripheral nervous system: an analysis of sciatic nerve and dorsal root ganglia."Dev.Biol. 155,459-70. PMID 8432400

[10] Erlandsson A, Enarsson M and Forsberg-Nilsson K.(2001)"Immature neurons from CNS stem cells proliferate in response to platelet-derived growth factor."J.Neurosci. 21,3483-91. PMID 11331377

[3MJG-1] PDB: 3MJG; Shim AH, Liu H, Focia PJ, Chen X, Lin PC, He X (June 2010). "Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex". Proceedings of the National Academy of Sciences of the United States of America. 107 (25): 11307–12. doi:10.1073/pnas.1000806107. PMC 2895058. PMID 20534510.; rendered using PyMOL.

[pmid2538922-2] Williams LT (March 1989). "Signal transduction by the platelet-derived growth factor receptor". Science. 243 (4898): 1564–70. doi:10.1126/science.2538922. PMID 2538922.

[pmid2543106-3] Heldin CH, Westermark B (April 1989). "Platelet-derived growth factor: three isoforms and two receptor types". Trends in Genetics. 5 (4): 108–11. doi:10.1016/0168-9525(89)90040-1. PMID 2543106.

[pmid1315403-4] Heldin CH, Ostman A, Eriksson A, Siegbahn A, Claesson-Welsh L, Westermark B (March 1992). "Platelet-derived growth factor: isoform-specific signalling via heterodimeric or homodimeric receptor complexes". Kidney International. 41 (3): 571–4. doi:10.1038/ki.1992.84. PMID 1315403.

[pmid18392794-5] Cao Y, Cao R, Hedlund EM (July 2008). "R Regulation of tumor angiogenesis and metastasis by FGF and PDGF signaling pathways". Journal of Molecular Medicine. 86 (7): 785–9. doi:10.1007/s00109-008-0337-z. PMID 18392794.

[pmid2550144-6] Kazlauskas A, Cooper JA (September 1989). "Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins". Cell. 58 (6): 1121–33. doi:10.1016/0092-8674(89)90510-2. PMID 2550144.

[pmid7682895-7] Valius M, Kazlauskas A (April 1993). "Phospholipase C-gamma 1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor's mitogenic signal". Cell. 73 (2): 321–34. doi:10.1016/0092-8674(93)90232-F. PMID 7682895.

[pmid9405485-8] Montmayeur JP, Valius M, Vandenheede J, Kazlauskas A (December 1997). "The platelet-derived growth factor beta receptor triggers multiple cytoplasmic signaling cascades that arrive at the nucleus as distinguishable inputs". The Journal of Biological Chemistry. 272 (51): 32670–8. doi:10.1074/jbc.272.51.32670. PMID 9405485.

[pmid24165129-9] Blazevic T, Schwaiberger AV, Schreiner CE, Schachner D, Schaible AM, Grojer CS, Atanasov AG, Werz O, Dirsch VM, Heiss EH (December 2013). "12/15-lipoxygenase contributes to platelet-derived growth factor-induced activation of signal transducer and activator of transcription 3". The Journal of Biological Chemistry. 288 (49): 35592–603. doi:10.1074/jbc.M113.489013. PMC 3853304. PMID 24165129.

[PMID_8193536-10] Schlessinger, J. SH2/SH3 Signaling Proteins. Curr. Op. Gen. Dev. 1994, 4(1):25-30.

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

リンク元	「イマチニブ」「モテサニブ」
関連記事	「PDGF」

匿名

検索

案内

PDGFR