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血小板衍生生長因子：修订间差异

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{{Redirect|PDGF|the space hardware|Power Data Grapple Fixture}}
{{Redirect|PDGF|航天器部件|锚钩固定装置}}
{{Infobox protein family
{{Pfam_box
| Symbol = PDGF
| Symbol = PDGF
| Name = 血小板衍生生長因子（PDGF）
| Name = 血小板衍生生長因子（PDGF）
| image =
| image = 1pdg.jpg
| width =
| width = 270
| caption =
| caption =
| Pfam= PF00341
| Pfam= PF00341
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| OPM protein=
| OPM protein=
}}
}}

'''血小板衍生生長因子'''（Platelet-derived growth factor，PDGF）為一種[[生長因子]]，可以調控[[細胞]]的生長和分化，且在[[血管新生]]上扮演重要角色。未控制的血管新生常常導致癌症。在化學上PDGF為[[醣蛋白]][[蛋白二聚體|二聚體]]，且有A和B兩種不同形式，可組合為AA、AB和BB等結構。
'''血小板衍生生長因子'''（Platelet-derived growth factor，PDGF）為一種[[生長因子]]，可以調控[[細胞]]的生長和分化，且在[[血管新生]]上扮演重要角色。未控制的血管新生常常導致癌症。在化學上PDGF為[[醣蛋白]][[蛋白二聚體|二聚體]]，且有A和B兩種不同形式，可組合為AA、AB和BB等結構。


PDGF<ref name="PUB00000590">{{cite journal | author = Hannink M, Donoghue DJ | title = Structure and function of platelet-derived growth factor (PDGF) and related proteins | journal = Biochim. Biophys. Acta | volume = 989 | issue = 1 | pages = 1–10 | year = 1989 | pmid = 2546599 | doi = 10.1016/0304-419x(89)90031-0 }}</ref><ref name="PUB00001228">{{cite journal | author = Heldin CH | title = Structural and functional studies on platelet-derived growth factor | journal = EMBO J. | volume = 11 | issue = 12 | pages = 4251–4259 | year = 1992 | pmid = 1425569 | pmc = 556997 }}</ref>是一種有效的[[间充质]]細胞[[丝裂原]]，包含[[平滑肌]]、[[神經膠細胞]]。
PDGF<ref name="PUB00000590">{{cite journal | author = Hannink M, Donoghue DJ | title = Structure and function of platelet-derived growth factor (PDGF) and related proteins | journal = Biochim. Biophys. Acta | volume = 989 | issue = 1 | pages = 1–10 | year = 1989 | pmid = 2546599 | doi = 10.1016/0304-419x(89)90031-0 }}</ref><ref name="PUB00001228">{{cite journal | author = Heldin CH | title = Structural and functional studies on platelet-derived growth factor | url = https://archive.org/details/sim_embo-journal_1992-12_11_12/page/4251 | journal = EMBO J. | volume = 11 | issue = 12 | pages = 4251–4259 | year = 1992 | pmid = 1425569 | pmc = 556997 }}</ref>是一種有效的[[间充质]]細胞[[丝裂原]]，包含[[纖維母細胞]]、[[平滑肌]]、[[神經膠細胞]]。在小鼠和人类中，PDGF信号网络都包括四種配体：PDGFA 到 PDGFAD，与两个受体:[[PDGFRA]]和[[PDGFRB]]。所有PDGF都表达到胞外，并通过[[二硫键]]连接形成同元二聚体，但只有PDGFA和B可以形成有功能的异元二聚体。


PDGF在被合成出來之後，會先貯存在血小板中的α顆粒當中<ref>{{cite web|title=The Basic Biology of Platelet Growth Factors|url=http://www.perfusion.com/cgi-bin/absolutenm/templates/articledisplay.asp?articleid=1678&|accessdate=2014-05-08|archive-date=2018-10-02|archive-url=https://web.archive.org/web/20181002151831/http://www.perfusion.com/cgi-bin/absolutenm/templates/articledisplay.asp?articleid=1678&|dead-url=no}}</ref>，直到受到刺激後才釋放出來。另外，平滑肌細胞、活化的巨噬細胞，和上皮細胞等多種細胞也會製造PDGF<ref>{{cite book|last=Kumar|first=Vinay|title=Robbins and Coltran Pathologic Basis of Disease|year=2010|publisher=Elsevier|location=China|isbn=978-1-4160-3121-5|pages=88–89}}</ref>。
在小鼠和人类中，PDGF信号网络都包括四个配体：PDGFA 到 PDGFAD，与两个受体:[[PDGFRA]]和[[PDGFRB]]。所有PDGF都表达到胞外，并通过[[二硫键]]连接形成同元二聚体，但只有PDGFA和B可以形成有功能的异元二聚体。

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{{TransH}}
Though it is synthesized,<ref>{{cite web|last=Minarcik|first=John|title=Global Path Course: Video|url=http://www.gopathdx.com/?action-model-name-lectures-itemid-69|accessdate=2011-06-27}}</ref> stored (in the alpha granules of platelets),<ref>{{cite web|title=The Basic Biology of Platelet Growth Factors|url=http://www.perfusion.com/cgi-bin/absolutenm/templates/articledisplay.asp?articleid=1678&|accessdate=2014-05-08}}</ref> and released by platelets upon activation, it is also produced by a plethora of cells including smooth muscle cells, activated macrophages, and endothelial cells<ref>{{cite book|last=Kumar|first=Vinay|title=Robbins and Coltran Pathologic Basis of Disease|year=2010|publisher=Elsevier|location=China|isbn=978-1-4160-3121-5|pages=88–89}}</ref>


醫療上，可使用[[重組DNA|合成]]PDGF加速{{le|潰瘍|Ulcer (dermatology)|慢性潰瘍}}病灶的癒合；骨科和牙周病專科上也會以PDGF治療骨質流失。
[[Recombinant DNA|Recombinant]] PDGF is used in medicine to help heal [[Ulcer (dermatology)|chronic ulcers]] and in orthopedic surgery and periodonistry to treat bone loss.


== 分類 ==
== 分類 ==
PDGF擁有五種{{le|亞型|isoform}}


⚫
{{TransH}}
There are five different [[isoform]]s of PDGF that activate cellular response through two different [[receptor (biochemistry)|receptors]]. Known [[ligand]]s include A (''[[PDGFA]]''), B (''[[PDGFB]]''), C (''[[PDGFC]]''), and D (''[[PDGFD]]''), and an AB hetero[[protein dimer|dimer]] and receptors alpha (''[[PDGFRA]]'') and beta (''[[PDGFRB]]''). PDGF has few other members of the family, for example [[VEGF sub-family]].
There are five different [[isoform]]s of PDGF that activate cellular response through two different [[受体 (生物化学)|receptors]]. Known [[配體|ligand]]s include A (''[[PDGFA]]''), B (''[[PDGFB]]''), C (''[[PDGFC]]''), and D (''[[PDGFD]]''), and an AB hetero[[蛋白二聚体|dimer]] and receptors alpha (''[[PDGFRA]]'') and beta (''[[PDGFRB]]''). PDGF has few other members of the family, for example [[血管内皮生长因子|VEGF sub-family]].


== 機制 ==
== 機制 ==


The [[Receptor (biochemistry)|receptor]] for PDGF, '''PDGFR''' is classified as a [[receptor tyrosine kinase]] (RTK), a type of [[plasma membrane|cell surface]] receptor. Two types of PDGFRs have been identified: alpha-type and beta-type PDGFRs.<ref>{{cite journal | author = Matsui T, Heidaran M, Miki T, Popescu N, La Rochelle W, Kraus M, Pierce J, Aaronson S | title = Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes | journal = Science | volume = 243 | issue = 4892 | pages = 800–4 | year = 1989 | pmid = 2536956 | doi = 10.1126/science.2536956 }}</ref> The alpha type binds to PDGF-AA, PDGF-BB and PDGF-AB, whereas the beta type PDGFR binds with high affinity to PDGF-BB and PDGF-AB.<ref>{{cite journal | author = Heidaran MA, Pierce JH, Yu JC, Lombardi D, Artrip JE, Fleming TP, Thomason A, Aaronson SA | title = Role of alpha beta receptor heterodimer formation in beta platelet-derived growth factor (PDGF) receptor activation by PDGF-AB | journal = J. Biol. Chem. | volume = 266 | issue = 30 | pages = 20232–7 | date = 25 October 1991 | pmid = 1657917 | url = http://www.jbc.org/cgi/content/abstract/266/30/20232 }}</ref>
The [[受体 (生物化学)|receptor]] for PDGF, '''PDGFR''' is classified as a [[receptor tyrosine kinase]] (RTK), a type of [[细胞膜|cell surface]] receptor. Two types of PDGFRs have been identified: alpha-type and beta-type PDGFRs.<ref>{{cite journal | author = Matsui T, Heidaran M, Miki T, Popescu N, La Rochelle W, Kraus M, Pierce J, Aaronson S | title = Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes | journal = Science | volume = 243 | issue = 4892 | pages = 800–4 | year = 1989 | pmid = 2536956 | doi = 10.1126/science.2536956 }}</ref> The alpha type binds to PDGF-AA, PDGF-BB and PDGF-AB, whereas the beta type PDGFR binds with high affinity to PDGF-BB and PDGF-AB.<ref>{{cite journal | author = Heidaran MA, Pierce JH, Yu JC, Lombardi D, Artrip JE, Fleming TP, Thomason A, Aaronson SA | title = Role of alpha beta receptor heterodimer formation in beta platelet-derived growth factor (PDGF) receptor activation by PDGF-AB | journal = J. Biol. Chem. | volume = 266 | issue = 30 | pages = 20232–7 | date = 25 October 1991 | pmid = 1657917 | url = http://www.jbc.org/cgi/content/abstract/266/30/20232 | access-date = 2015-05-24 | archive-date = 2008-11-05 | archive-url = https://web.archive.org/web/20081105205653/http://www.jbc.org/cgi/content/abstract/266/30/20232 | dead-url = yes }}</ref>
PDGF binds to PDGFRs ligand binding pocket located within the second and third immunoglobulin domains.<ref>{{cite journal | author = Heidaran MA, Pierce JH, Jensen RA, Matsui T, Aaronson SA | title = Chimeric alpha- and beta-platelet-derived growth factor (PDGF) receptors define three immunoglobulin-like domains of the alpha-PDGF receptor that determine PDGF-AA binding specificity | journal = J. Biol. Chem. | volume = 265 | issue = 31 | pages = 18741–4 | date = 5 November 1990 | pmid = 2172231 | url = http://www.jbc.org/cgi/content/abstract/265/31/18741 }}</ref> Upon activation by PDGF, these receptors dimerise, and are "switched on" by auto-[[phosphorylation]] of several sites on their [[cytosol]]ic domains, which serve to mediate binding of cofactors and subsequently activate [[signal transduction]], for example, through the [[Phosphoinositide 3-kinase|PI3K]] pathway or through [[reactive oxygen species (ROS)]]-mediated activation of the [[STAT3]] pathway.<ref name="pmid24165129">{{cite journal | author = Blazevic T, Schwaiberger AV, Schreiner CE, Schachner D, Schaible AM, Grojer CS, Atanasov AG, Werz O, Dirsch VM, Heiss EH | title = 12/15-Lipoxygenase Contributes to Platelet-derived Growth Factor-induced Activation of Signal Transducer and Activator of Transcription 3 | journal = J. Biol. Chem. | volume = 288 | issue = 49 | pages = 35592–603 | date = December 2013 | pmid = 24165129 | pmc = 3853304 | doi = 10.1074/jbc.M113.489013 }}</ref> Downstream effects of this include regulation of [[gene expression]] and the [[cell cycle]].
PDGF binds to the PDGFR ligand binding pocket located within the second and third immunoglobulin domains.<ref>{{cite journal | author = Heidaran MA, Pierce JH, Jensen RA, Matsui T, Aaronson SA | title = Chimeric alpha- and beta-platelet-derived growth factor (PDGF) receptors define three immunoglobulin-like domains of the alpha-PDGF receptor that determine PDGF-AA binding specificity | journal = J. Biol. Chem. | volume = 265 | issue = 31 | pages = 18741–4 | date = 5 November 1990 | pmid = 2172231 | url = http://www.jbc.org/cgi/content/abstract/265/31/18741 | access-date = 2015-05-24 | archive-date = 2008-07-25 | archive-url = https://web.archive.org/web/20080725034256/http://www.jbc.org/cgi/content/abstract/265/31/18741 | dead-url = yes }}</ref> Upon activation by PDGF, these receptors dimerise, and are "switched on" by auto-[[磷酸化|phosphorylation]] of several sites on their [[细胞质基质|cytosol]]ic domains, which serve to mediate binding of cofactors and subsequently activate [[訊息傳遞 (生物)|signal transduction]], for example, through the [[Phosphoinositide 3-kinase|PI3K]] pathway or through [[reactive oxygen species (ROS)]]-mediated activation of the [[STAT3]] pathway.<ref name="pmid24165129">{{cite journal | author = Blazevic T, Schwaiberger AV, Schreiner CE, Schachner D, Schaible AM, Grojer CS, Atanasov AG, Werz O, Dirsch VM, Heiss EH | title = 12/15-Lipoxygenase Contributes to Platelet-derived Growth Factor-induced Activation of Signal Transducer and Activator of Transcription 3 | journal = J. Biol. Chem. | volume = 288 | issue = 49 | pages = 35592–603 | date = December 2013 | pmid = 24165129 | pmc = 3853304 | doi = 10.1074/jbc.M113.489013 }}</ref> Downstream effects of this include regulation of [[基因表現|gene expression]] and the [[細胞週期|cell cycle]].
The role of PI3K has been investigated by several laboratories. Accumulating data suggests that, while this molecule is, in general, part of growth signaling complex, it plays a more profound role in controlling cell migration.<ref>{{cite journal | author = Yu JC, Li W, Wang LM, Uren A, Pierce JH, Heidaran MA | title = Differential requirement of a motif within the carboxyl-terminal domain of alpha-platelet-derived growth factor (alpha PDGF) receptor for PDGF focus forming activity chemotaxis, or growth | journal = J. Biol. Chem. | volume = 270 | issue = 13 | pages = 7033–6 | year = 1995 | pmid = 7706238 | doi = 10.1074/jbc.270.13.7033 }}</ref>
The role of PI3K has been investigated by several laboratories. Accumulating data suggests that, while this molecule is, in general, part of growth signaling complex, it plays a more profound role in controlling cell migration.<ref>{{cite journal | author = Yu JC, Li W, Wang LM, Uren A, Pierce JH, Heidaran MA | title = Differential requirement of a motif within the carboxyl-terminal domain of alpha-platelet-derived growth factor (alpha PDGF) receptor for PDGF focus forming activity chemotaxis, or growth | journal = J. Biol. Chem. | volume = 270 | issue = 13 | pages = 7033–6 | year = 1995 | pmid = 7706238 | doi = 10.1074/jbc.270.13.7033 }}</ref>
The different ligand isoforms have variable affinities for the receptor isoforms, and the receptor isoforms may variably form hetero- or homo- dimers. This leads to specificity of downstream signaling. It has been shown that the ''sis'' [[oncogene]] is derived from the PDGF B-chain [[gene]]. PDGF-BB is the highest-affinity ligand for the PDGFR-beta; PDGFR-beta is a key marker of hepatic stellate cell activation in the process of [[fibrogenesis]].{{Citation needed|date=April 2007}}
The different ligand isoforms have variable affinities for the receptor isoforms, and the receptor isoforms may variably form hetero- or homo- dimers. This leads to specificity of downstream signaling. It has been shown that the ''sis'' [[癌基因|oncogene]] is derived from the PDGF B-chain [[基因|gene]]. PDGF-BB is the highest-affinity ligand for the PDGFR-beta; PDGFR-beta is a key marker of hepatic stellate cell activation in the process of [[纤维化|fibrogenesis]].{{Citation needed|date=April 2007}}


== 功能 ==
== 功能 ==


PDGFs are mitogenic during early developmental stages,driving the proliferation of undifferentiated [[mesenchyme]] and some [[progenitor]] populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis.In addition to driving mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the adult animal.<ref name="PUB00014075">{{cite journal | author = Hoch RV, Soriano P | title = Roles of PDGF in animal development | journal = Development | volume = 130 | issue = 20 | pages = 4769–4784 | year = 2003 | pmid = 12952899 | doi = 10.1242/dev.00721 }}</ref> Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C)<ref name="PUB00004886">{{cite journal | author = Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U | title = Vascular endothelial growth factor B, a novel growth factor for endothelial cells | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 6 | pages = 2567–2581 | year = 1996 | pmid = 8637916 | pmc = 39839 | doi = 10.1073/pnas.93.6.2576 }}</ref><ref name="PUB00001288">{{cite journal | author = Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K | title = A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases | journal = EMBO J. | volume = 15 | issue = 2 | pages = 290–298 | year = 1996 | pmid = 8617204 | pmc = 449944 }}</ref> which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis.<ref name="PUB00004494">{{cite journal | author = Maglione D, Guerriero V, Viglietto G, Ferraro MG, Aprelikova O, Alitalo K, Del Vecchio S, Lei KJ, Chou JY, Persico MG | title = Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14 | journal = Oncogene | volume = 8 | issue = 4 | pages = 925–931 | year = 1993 | pmid = 7681160 }}</ref>
PDGFs are mitogenic during early developmental stages, driving the proliferation of undifferentiated [[间充质|mesenchyme]] and some [[progenitor]] populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis. In addition to driving mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the adult animal.<ref name="PUB00014075">{{cite journal | author = Hoch RV, Soriano P | title = Roles of PDGF in animal development | journal = Development | volume = 130 | issue = 20 | pages = 4769–4784 | year = 2003 | pmid = 12952899 | doi = 10.1242/dev.00721 }}</ref> Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C)<ref name="PUB00004886">{{cite journal | author = Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U | title = Vascular endothelial growth factor B, a novel growth factor for endothelial cells | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 6 | pages = 2567–2581 | year = 1996 | pmid = 8637916 | pmc = 39839 | doi = 10.1073/pnas.93.6.2576 }}</ref><ref name="PUB00001288">{{cite journal | author = Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K | title = A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases | journal = EMBO J. | volume = 15 | issue = 2 | pages = 290–298 | year = 1996 | pmid = 8617204 | pmc = 449944 }}</ref> which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis.<ref name="PUB00004494">{{cite journal | author = Maglione D, Guerriero V, Viglietto G, Ferraro MG, Aprelikova O, Alitalo K, Del Vecchio S, Lei KJ, Chou JY, Persico MG | title = Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14 | url = https://archive.org/details/sim_oncogene_1993-04_8_4/page/925 | journal = Oncogene | volume = 8 | issue = 4 | pages = 925–931 | year = 1993 | pmid = 7681160 }}</ref>


PDGF plays a role in [[embryo]]nic development, cell proliferation, cell migration, and [[angiogenesis]].<ref>{{cite web |url=http://www.multi-targetedtherapy.com/pdgfSignaling.asp |title=PDGF Pathways |accessdate=2007-11-17}}</ref> Over-expression of PDGF has been linked to several [[disease]]s such as [[atherosclerosis]], fibrotic disorders and malignancies. Synthesis occurs due to external stimuli such as thrombin, low oxygen tension, or other cytokines and growth factors.<ref name="pmid16970222">{{cite journal | author = Alvarez RH, Kantarjian HM, Cortes JE | title = Biology of platelet-derived growth factor and its involvement in disease | journal = Mayo Clin. Proc. | volume = 81 | issue = 9 | pages = 1241–57 | date = September 2006 | pmid = 16970222 | doi = 10.4065/81.9.1241 }}</ref>
PDGF plays a role in [[胚胎|embryo]]nic development, cell proliferation, cell migration, and [[血管新生|angiogenesis]].<ref>{{cite web |url=http://www.multi-targetedtherapy.com/pdgfSignaling.asp |title=PDGF Pathways |accessdate=2007-11-17 |deadurl=yes |archiveurl=https://web.archive.org/web/20061113131941/http://www.multi-targetedtherapy.com/pdgfSignaling.asp |archivedate=2006-11-13 }}</ref> Over-expression of PDGF has been linked to several [[疾病|disease]]s such as [[动脉粥样硬化|atherosclerosis]], fibrotic disorders and malignancies. Synthesis occurs due to external stimuli such as thrombin, low oxygen tension, or other cytokines and growth factors.<ref name="pmid16970222">{{cite journal | author = Alvarez RH, Kantarjian HM, Cortes JE | title = Biology of platelet-derived growth factor and its involvement in disease | url = https://archive.org/details/sim_mayo-clinic-proceedings_2006-09_81_9/page/1241 | journal = Mayo Clin. Proc. | volume = 81 | issue = 9 | pages = 1241–57 | date = September 2006 | pmid = 16970222 | doi = 10.4065/81.9.1241 }}</ref>


PDGF is a required element in cellular division for [[fibroblasts]], a type of connective tissue cell that is especially prevalent in wound healing.<ref name="pmid16970222"/> In essence, the PDGFs allow a cell to skip the [[cell cycle|G1 checkpoints]] in order to divide.<ref name="pmid15784165">{{cite journal | author = Song G, Ouyang G, Bao S | title = The activation of Akt/PKB signaling pathway and cell survival | journal = J. Cell. Mol. Med. | volume = 9 | issue = 1 | pages = 59–71 | year = 2005 | pmid = 15784165 | doi = 10.1111/j.1582-4934.2005.tb00337.x }}</ref> It has been shown that in monocytes-macrophages and fibroblasts, exogenously administered PDGF stimulates chemotaxis, proliferation, and gene expression and significantly augmented the influx of inflammatory cells and fibroblasts, accelerating extracellular matrix and collagen formation and thus reducing the time for the healing process to occur.<ref name="pmid2045423">{{cite journal | author = Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A | title = Role of platelet-derived growth factor in wound healing | journal = J. Cell. Biochem. | volume = 45 | issue = 4 | pages = 319–26 | date = April 1991 | pmid = 2045423 | doi = 10.1002/jcb.240450403 }}</ref>
PDGF is a required element in cellular division for [[成纤维细胞|fibroblasts]], a type of connective tissue cell that is especially prevalent in wound healing.<ref name="pmid16970222"/> In essence, the PDGFs allow a cell to skip the [[細胞週期|G1 checkpoints]] in order to divide.<ref name="pmid15784165">{{cite journal | author = Song G, Ouyang G, Bao S | title = The activation of Akt/PKB signaling pathway and cell survival | journal = J. Cell. Mol. Med. | volume = 9 | issue = 1 | pages = 59–71 | year = 2005 | pmid = 15784165 | doi = 10.1111/j.1582-4934.2005.tb00337.x }}</ref> It has been shown that in monocytes-macrophages and fibroblasts, exogenously administered PDGF stimulates chemotaxis, proliferation, and gene expression and significantly augmented the influx of inflammatory cells and fibroblasts, accelerating extracellular matrix and collagen formation and thus reducing the time for the healing process to occur.<ref name="pmid2045423">{{cite journal | author = Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A | title = Role of platelet-derived growth factor in wound healing | url = https://archive.org/details/sim_journal-of-cellular-biochemistry_1991-04_45_4/page/319 | journal = J. Cell. Biochem. | volume = 45 | issue = 4 | pages = 319–26 | date = April 1991 | pmid = 2045423 | doi = 10.1002/jcb.240450403 }}</ref>


In terms of osteogenic differentiation of mesenchymal stem cells, comparing PDGF to epidermal growth factor (EGF), which is also implicated in stimulating cell growth, proliferation, and differentiation,<ref name="Kratchmarova, I 2005" /> MSCs were shown to have stronger osteogenic differentiation into bone-forming cells when stimulated by epidermal growth factor (EGF) versus PDGF. However, comparing the signaling pathways between them reveals that the PI3K pathway is exclusively activated by PDGF, with EGF having no effect. Chemically inhibiting the PI3K pathway in PDGF-stimulated cells negates the differential effect between the two growth factors, and actually gives PDGF an edge in osteogenic differentiation.<ref name="Kratchmarova, I 2005">{{cite journal | author = Kratchmarova I, Blagoev B, Haack-Sorensen M, Kassem M, Mann M | title = Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation | journal = Science | volume = 308 | issue = 5727 | pages = 1472–7 | date = June 2005 | pmid = 15933201 | doi = 10.1126/science.1107627 }}</ref> [[Wortmannin]] is a PI3K-specific inhibitor, and treatment of cells with Wortmannin in combination with PDGF resulted in enhanced osteoblast differentiation compared to just PDGF alone, as well as compared to EGF.<ref name="Kratchmarova, I 2005"/> These results indicate that the addition of Wortmannin can significantly increase the response of cells into an osteogenic lineage in the presence of PDGF, and thus might reduce the need for higher concentrations of PDGF or other growth factors, making PDGF a more viable growth factor for osteogenic differentiation than other, more expensive growth factors currently used in the field such as BMP2.<ref>Hayashi, A. The New Standard of Care for Nonunions?. AAOS Now. 2009.</ref>
In terms of osteogenic differentiation of mesenchymal stem cells, comparing PDGF to epidermal growth factor (EGF), which is also implicated in stimulating cell growth, proliferation, and differentiation,<ref name="Kratchmarova, I 2005" /> MSCs were shown to have stronger osteogenic differentiation into bone-forming cells when stimulated by epidermal growth factor (EGF) versus PDGF. However, comparing the signaling pathways between them reveals that the PI3K pathway is exclusively activated by PDGF, with EGF having no effect. Chemically inhibiting the PI3K pathway in PDGF-stimulated cells negates the differential effect between the two growth factors, and actually gives PDGF an edge in osteogenic differentiation.<ref name="Kratchmarova, I 2005">{{cite journal | author = Kratchmarova I, Blagoev B, Haack-Sorensen M, Kassem M, Mann M | title = Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation | journal = Science | volume = 308 | issue = 5727 | pages = 1472–7 | date = June 2005 | pmid = 15933201 | doi = 10.1126/science.1107627 }}</ref> [[Wortmannin]] is a PI3K-specific inhibitor, and treatment of cells with Wortmannin in combination with PDGF resulted in enhanced osteoblast differentiation compared to just PDGF alone, as well as compared to EGF.<ref name="Kratchmarova, I 2005"/> These results indicate that the addition of Wortmannin can significantly increase the response of cells into an osteogenic lineage in the presence of PDGF, and thus might reduce the need for higher concentrations of PDGF or other growth factors, making PDGF a more viable growth factor for osteogenic differentiation than other, more expensive growth factors currently used in the field such as BMP2.<ref>Hayashi, A. The New Standard of Care for Nonunions?. AAOS Now. 2009.</ref>
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== 歷史 ==
== 歷史 ==


PDGF was one of the first [[growth factor]]s characterized,<ref>{{cite journal | author = Paul D, Lipton A, Klinger I | title = Serum factor requirements of normal and simian virus 40-transformed 3T3 mouse fibroplasts | journal = Proc Natl Acad Sci U S A. | volume = 68 | issue = 3 | pages = 645–52 | year = 1971 | pmid = 5276775 | pmc = 389008 | doi = 10.1073/pnas.68.3.645 }}</ref> and has led to an understanding of the mechanism of many growth factor [[biochemical signaling|signaling pathways]].{{Citation needed|date=April 2007}}
PDGF是第一种被鉴定的[[生长因子]]<ref>{{cite journal | author = Paul D, Lipton A, Klinger I | title = Serum factor requirements of normal and simian virus 40-transformed 3T3 mouse fibroplasts | journal = Proc Natl Acad Sci U S A. | volume = 68 | issue = 3 | pages = 645–52 | year = 1971 | pmid = 5276775 | pmc = 389008 | doi = 10.1073/pnas.68.3.645 }}</ref>，引领了许多生长因子[[訊息傳遞 (生物)|信号通路的研究]]{{Citation needed|date=April 2007}}。



==藥物==
==藥物==

[[Recombinant DNA|Recombinant]] PDGF is used to help heal [[Ulcer (dermatology)|chronic ulcers]] and in orthopedic surgery and periodonistry to treat bone loss.<ref>Friedlaender GE et al. The Role of Recombinant Human Platelet-derived Growth Factor-BB (rhPDGF-BB) in Orthopaedic Bone Repair and Regeneration Curr Pharm Des. 2013;19(19):3384-90. PMID 23432673. Quote: "Demonstration of the safety and efficacy of rhPDGF-BB in the healing of chronic foot ulcers in diabetic patients and regeneration of alveolar (jaw) bone lost due to chronic infection from periodontal disease has resulted in two FDA-approved products based on this molecule"</ref>
[[重組DNA|Recombinant]] PDGF is used to help heal [[Ulcer (dermatology)|chronic ulcers]] and in orthopedic surgery and periodontistry to treat bone loss.<ref>Friedlaender GE et al. The Role of Recombinant Human Platelet-derived Growth Factor-BB (rhPDGF-BB) in Orthopaedic Bone Repair and Regeneration Curr Pharm Des. 2013;19(19):3384-90. PMID 23432673. Quote: "Demonstration of the safety and efficacy of rhPDGF-BB in the healing of chronic foot ulcers in diabetic patients and regeneration of alveolar (jaw) bone lost due to chronic infection from periodontal disease has resulted in two FDA-approved products based on this molecule"</ref>


== 研究 ==
== 研究 ==


Like many other growth factors that have been linked to disease, PDGF and its receptors have provided a market for [[receptor antagonist]]s to treat disease. Such antagonists include (but are not limited to) specific [[antibody|antibodies]] that target the [[molecule]] of interest, which act only in a neutralizing manner.<ref name="pmid9211881">{{cite journal | author = Shulman T, Sauer FG, Jackman RM, Chang CN, Landolfi NF | title = An antibody reactive with domain 4 of the platelet-derived growth factor beta receptor allows BB binding while inhibiting proliferation by impairing receptor dimerization | journal = J. Biol. Chem. | volume = 272 | issue = 28 | pages = 17400–4 | date = July 1997 | pmid = 9211881 | doi = 10.1074/jbc.272.28.17400 | url = }}</ref>
Like many other growth factors that have been linked to disease, PDGF and its receptors have provided a market for [[受体拮抗剂|receptor antagonist]]s to treat disease. Such antagonists include (but are not limited to) specific [[抗体|antibodies]] that target the [[分子|molecule]] of interest, which act only in a neutralizing manner.<ref name="pmid9211881">{{cite journal | author = Shulman T, Sauer FG, Jackman RM, Chang CN, Landolfi NF | title = An antibody reactive with domain 4 of the platelet-derived growth factor beta receptor allows BB binding while inhibiting proliferation by impairing receptor dimerization | journal = J. Biol. Chem. | volume = 272 | issue = 28 | pages = 17400–4 | date = July 1997 | pmid = 9211881 | doi = 10.1074/jbc.272.28.17400 | url = }}</ref>


The "c-Sis" [[oncogene]] is derived from PDGF.<ref name="ReferenceA"/><ref>{{cite journal | author = McClintock JT, Chan IJ, Thaker SR, Katial A, Taub FE, Aotaki-Keen AE, Hjelmeland LM | title = Detection of c-sis proto-oncogene transcripts by direct enzyme-labeled cDNA probes and in situ hybridization | journal = In Vitro Cell Dev Biol | volume = 28A | issue = 2 | pages = 102–8 | year = 1992 | pmid = 1537750 | doi = 10.1007/BF02631013 }}</ref>
The "c-Sis" [[癌基因|oncogene]] is derived from PDGF.<ref name="ReferenceA"/><ref>{{cite journal | author = McClintock JT, Chan IJ, Thaker SR, Katial A, Taub FE, Aotaki-Keen AE, Hjelmeland LM | title = Detection of c-sis proto-oncogene transcripts by direct enzyme-labeled cDNA probes and in situ hybridization | url = https://archive.org/details/sim_in-vitro-cellular-developmental-biology_1992-02_28a_2/page/102 | journal = In Vitro Cell Dev Biol | volume = 28A | issue = 2 | pages = 102–8 | year = 1992 | pmid = 1537750 | doi = 10.1007/BF02631013 }}</ref>


Age related downregulation of the PDGF receptor on islet beta cells has been demonstrated to prevent islet beta cell proliferation in both animal and human cells and its re-expression triggered beta cell proliferation and corrected glucose regulation via insulin secretion.<ref>{{cite web|url=http://www.eurekalert.org/pub_releases/2011-10/jdrf-rmo101211.php |title=Researchers make older beta cells act young again |publisher=Eurekalert.org |date=2011-10-12 |accessdate=2013-12-28}}</ref><ref>{{cite web|url=http://med.stanford.edu/ism/2011/october/kim.html |title=New Stanford molecular target for diabetes treatment discovered - Office of Communications & Public Affairs - Stanford University School of Medicine |publisher=Med.stanford.edu |date=2011-10-12 |accessdate=2013-12-28}}</ref>
Age related downregulation of the PDGF receptor on islet beta cells has been demonstrated to prevent islet beta cell proliferation in both animal and human cells and its re-expression triggered beta cell proliferation and corrected glucose regulation via insulin secretion.<ref>{{cite web |url=http://www.eurekalert.org/pub_releases/2011-10/jdrf-rmo101211.php |title=Researchers make older beta cells act young again |publisher=Eurekalert.org |date=2011-10-12 |accessdate=2013-12-28 |archive-date=2018-12-12 |archive-url=https://web.archive.org/web/20181212045222/https://www.eurekalert.org/pub_releases/2011-10/jdrf-rmo101211.php |dead-url=no }}</ref><ref>{{cite web |url=http://med.stanford.edu/ism/2011/october/kim.html |title=New Stanford molecular target for diabetes treatment discovered - Office of Communications & Public Affairs - Stanford University School of Medicine |publisher=Med.stanford.edu |date=2011-10-12 |accessdate=2013-12-28 |deadurl=yes |archiveurl=https://web.archive.org/web/20131021184626/http://med.stanford.edu/ism/2011/october/kim.html |archivedate=2013-10-21 }}</ref>


A non-viral PDGF "bio patch" can regenerate missing or damaged bone by delivering DNA in a nano-sized particle directly into cells via genes. Repairing bone fractures, fixing craniofacial defects and improving dental implants are among potential uses. The patch employs a collagen platform seeded with particles containing the genes needed for producing bone. In experiments, it new bone fully covered skull wounds in test animals and stimulated growth in human bone marrow [[stromal cell]]s.<ref>{{cite web|url=http://www.kurzweilai.net/bio-patch-can-regrow-bone-for-dental-implants-and-craniofacial-defects |title=Bio patch can regrow bone for dental implants and craniofacial defects |doi=10.1016/j.biomaterials.2013.10.021 |publisher=KurzweilAI |date=2013-11-12 |accessdate=2013-12-28}}</ref><ref>{{cite journal | author = Elangovan S, D'Mello SR, Hong L, Ross RD, Allamargot C, Dawson DV, Stanford CM, Johnson GK, Sumner DR, Salem AK | title = The enhancement of bone regeneration by gene activated matrix encoding for platelet derived growth factor | journal = Biomaterials | volume = 35 | issue = 2 | pages = 737–747 | year = 2014 | pmid = 24161167 | pmc = 3855224 | doi = 10.1016/j.biomaterials.2013.10.021 }}</ref>
A non-viral PDGF "bio patch" can regenerate missing or damaged bone by delivering DNA in a nano-sized particle directly into cells via genes. Repairing bone fractures, fixing craniofacial defects and improving dental implants are among potential uses. The patch employs a collagen platform seeded with particles containing the genes needed for producing bone. In experiments, it new bone fully covered skull wounds in test animals and stimulated growth in human bone marrow [[基质细胞|stromal cell]]s.<ref>{{cite web |url=http://www.kurzweilai.net/bio-patch-can-regrow-bone-for-dental-implants-and-craniofacial-defects |title=Bio patch can regrow bone for dental implants and craniofacial defects |doi=10.1016/j.biomaterials.2013.10.021 |publisher=KurzweilAI |date=2013-11-12 |accessdate=2013-12-28 |archive-date=2021-01-26 |archive-url=https://web.archive.org/web/20210126071400/https://www.kurzweilai.net/bio-patch-can-regrow-bone-for-dental-implants-and-craniofacial-defects |dead-url=no }}</ref><ref>{{cite journal | author = Elangovan S, D'Mello SR, Hong L, Ross RD, Allamargot C, Dawson DV, Stanford CM, Johnson GK, Sumner DR, Salem AK | title = The enhancement of bone regeneration by gene activated matrix encoding for platelet derived growth factor | journal = Biomaterials | volume = 35 | issue = 2 | pages = 737–747 | year = 2014 | pmid = 24161167 | pmc = 3855224 | doi = 10.1016/j.biomaterials.2013.10.021 }}</ref>


== PDGF家族 ==
== PDGF家族 ==
第74行： 第72行：
* [[PDGFA]]; [[PDGFB]]; [[PDGFC]]; [[PDGFD]]
* [[PDGFA]]; [[PDGFB]]; [[PDGFC]]; [[PDGFD]]
* [[Placental growth factor|PGF]]
* [[Placental growth factor|PGF]]
* [[Vascular endothelial growth factor|VEGF]]; [[VEGF41]]; [[Vascular endothelial growth factor B|VEGFB]]; [[Vascular endothelial growth factor C|VEGFC]];
* [[血管内皮生长因子|VEGF]]; [[VEGF41]]; [[Vascular endothelial growth factor B|VEGFB]]; [[Vascular endothelial growth factor C|VEGFC]];


== 參見 ==
== 參見 ==
* [[Platelet-activating factor]]
* [[Platelet-activating factor]]
* [[Platelet-derived growth factor receptor]]
* [[血小板衍生生長因子受體|Platelet-derived growth factor receptor]]
* [[atheroma]] platelet involvement in smooth muscle proliferation
* [[atheroma]] platelet involvement in smooth muscle proliferation
* [[Withaferin A]] potent inhibitor of angiogenesis
* [[Withaferin A]] potent inhibitor of angiogenesis


⚫
{{TransF}}
== 參考文獻 ==
== 參考文獻 ==
{{Reflist|35em}}
{{Reflist|2}}


== 外部連結 ==
== 外部連結 ==
* {{MeshName|platelet-derived+growth+factor}}
* {{MeshName|platelet-derived+growth+factor}}

⚫
{{TransF}}
{{生长因子}}
{{Signaling proteins}}
{{抑癌基因与癌基因}}
{{Oncogenes}}


{{DEFAULTSORT:Platelet-Derived Growth Factor}}
{{DEFAULTSORT:Platelet-Derived Growth Factor}}

2022年9月27日 (二) 09:01的最新版本

「PDGF」重定向至此。关于航天器部件，请见「锚钩固定装置」。
血小板衍生生長因子（PDGF）
鑑定
標誌PDGF
PfamPF00341（旧版）
InterPro（英语：InterPro）IPR000072
PROSITE（英语：PROSITE）PDOC00222
SCOP（英语：Structural Classification of Proteins）1pdg / SUPFAM

血小板衍生生長因子（Platelet-derived growth factor，PDGF）為一種生長因子，可以調控細胞的生長和分化，且在血管新生上扮演重要角色。未控制的血管新生常常導致癌症。在化學上PDGF為醣蛋白二聚體，且有A和B兩種不同形式，可組合為AA、AB和BB等結構。

PDGF[1][2]是一種有效的间充质細胞丝裂原，包含纖維母細胞、平滑肌、神經膠細胞。在小鼠和人类中，PDGF信号网络都包括四種配体：PDGFA 到 PDGFAD，与两个受体:PDGFRA和PDGFRB。所有PDGF都表达到胞外，并通过二硫键连接形成同元二聚体，但只有PDGFA和B可以形成有功能的异元二聚体。

PDGF在被合成出來之後，會先貯存在血小板中的α顆粒當中[3]，直到受到刺激後才釋放出來。另外，平滑肌細胞、活化的巨噬細胞，和上皮細胞等多種細胞也會製造PDGF[4]。

醫療上，可使用合成PDGF加速慢性潰瘍病灶的癒合；骨科和牙周病專科上也會以PDGF治療骨質流失。

分類

[编辑]

PDGF擁有五種亞型（英语：isoform）

已隱藏部分未翻譯内容，歡迎參與翻譯。

There are five different isoforms of PDGF that activate cellular response through two different receptors. Known ligands include A (PDGFA), B (PDGFB), C (PDGFC), and D (PDGFD), and an AB heterodimer and receptors alpha (PDGFRA) and beta (PDGFRB). PDGF has few other members of the family, for example VEGF sub-family.

機制

[编辑]

The receptor for PDGF, PDGFR is classified as a receptor tyrosine kinase (RTK), a type of cell surface receptor. Two types of PDGFRs have been identified: alpha-type and beta-type PDGFRs.[5] The alpha type binds to PDGF-AA, PDGF-BB and PDGF-AB, whereas the beta type PDGFR binds with high affinity to PDGF-BB and PDGF-AB.[6] PDGF binds to the PDGFR ligand binding pocket located within the second and third immunoglobulin domains.[7] Upon activation by PDGF, these receptors dimerise, and are "switched on" by auto-phosphorylation of several sites on their cytosolic domains, which serve to mediate binding of cofactors and subsequently activate signal transduction, for example, through the PI3K pathway or through reactive oxygen species (ROS)-mediated activation of the STAT3 pathway.[8] Downstream effects of this include regulation of gene expression and the cell cycle. The role of PI3K has been investigated by several laboratories. Accumulating data suggests that, while this molecule is, in general, part of growth signaling complex, it plays a more profound role in controlling cell migration.[9] The different ligand isoforms have variable affinities for the receptor isoforms, and the receptor isoforms may variably form hetero- or homo- dimers. This leads to specificity of downstream signaling. It has been shown that the sis oncogene is derived from the PDGF B-chain gene. PDGF-BB is the highest-affinity ligand for the PDGFR-beta; PDGFR-beta is a key marker of hepatic stellate cell activation in the process of fibrogenesis.[來源請求]

功能

[编辑]

PDGFs are mitogenic during early developmental stages, driving the proliferation of undifferentiated mesenchyme and some progenitor populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis. In addition to driving mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the adult animal.[10] Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C)[11][12] which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis.[13]

PDGF plays a role in embryonic development, cell proliferation, cell migration, and angiogenesis.[14] Over-expression of PDGF has been linked to several diseases such as atherosclerosis, fibrotic disorders and malignancies. Synthesis occurs due to external stimuli such as thrombin, low oxygen tension, or other cytokines and growth factors.[15]

PDGF is a required element in cellular division for fibroblasts, a type of connective tissue cell that is especially prevalent in wound healing.[15] In essence, the PDGFs allow a cell to skip the G1 checkpoints in order to divide.[16] It has been shown that in monocytes-macrophages and fibroblasts, exogenously administered PDGF stimulates chemotaxis, proliferation, and gene expression and significantly augmented the influx of inflammatory cells and fibroblasts, accelerating extracellular matrix and collagen formation and thus reducing the time for the healing process to occur.[17]

In terms of osteogenic differentiation of mesenchymal stem cells, comparing PDGF to epidermal growth factor (EGF), which is also implicated in stimulating cell growth, proliferation, and differentiation,[18] MSCs were shown to have stronger osteogenic differentiation into bone-forming cells when stimulated by epidermal growth factor (EGF) versus PDGF. However, comparing the signaling pathways between them reveals that the PI3K pathway is exclusively activated by PDGF, with EGF having no effect. Chemically inhibiting the PI3K pathway in PDGF-stimulated cells negates the differential effect between the two growth factors, and actually gives PDGF an edge in osteogenic differentiation.[18] Wortmannin is a PI3K-specific inhibitor, and treatment of cells with Wortmannin in combination with PDGF resulted in enhanced osteoblast differentiation compared to just PDGF alone, as well as compared to EGF.[18] These results indicate that the addition of Wortmannin can significantly increase the response of cells into an osteogenic lineage in the presence of PDGF, and thus might reduce the need for higher concentrations of PDGF or other growth factors, making PDGF a more viable growth factor for osteogenic differentiation than other, more expensive growth factors currently used in the field such as BMP2.[19]

PDGF is also known to maintain proliferation of oligodendrocyte progenitor cells.[20][21] It has also been shown that fibroblast growth factor (FGF) activates a signaling pathway that positively regulates the PDGF receptors in oligodendrocyte progenitor cells.[22]

歷史

[编辑]

PDGF是第一种被鉴定的生长因子[23]，引领了许多生长因子信号通路的研究[來源請求]。

藥物

[编辑]

Recombinant PDGF is used to help heal chronic ulcers and in orthopedic surgery and periodontistry to treat bone loss.[24]

研究

[编辑]

Like many other growth factors that have been linked to disease, PDGF and its receptors have provided a market for receptor antagonists to treat disease. Such antagonists include (but are not limited to) specific antibodies that target the molecule of interest, which act only in a neutralizing manner.[25]

The "c-Sis" oncogene is derived from PDGF.[21][26]

Age related downregulation of the PDGF receptor on islet beta cells has been demonstrated to prevent islet beta cell proliferation in both animal and human cells and its re-expression triggered beta cell proliferation and corrected glucose regulation via insulin secretion.[27][28]

A non-viral PDGF "bio patch" can regenerate missing or damaged bone by delivering DNA in a nano-sized particle directly into cells via genes. Repairing bone fractures, fixing craniofacial defects and improving dental implants are among potential uses. The patch employs a collagen platform seeded with particles containing the genes needed for producing bone. In experiments, it new bone fully covered skull wounds in test animals and stimulated growth in human bone marrow stromal cells.[29][30]

PDGF家族

[编辑]

Human genes encoding proteins that belong to the platelet-derived growth factor family include:

參見

[编辑]

參考文獻

[编辑]
  1. ^ Hannink M, Donoghue DJ. Structure and function of platelet-derived growth factor (PDGF) and related proteins. Biochim. Biophys. Acta. 1989, 989 (1): 1–10. PMID 2546599. doi:10.1016/0304-419x(89)90031-0. 
  2. ^ Heldin CH. Structural and functional studies on platelet-derived growth factor. EMBO J. 1992, 11 (12): 4251–4259. PMC 556997 可免费查阅. PMID 1425569. 
  3. ^ The Basic Biology of Platelet Growth Factors. [2014-05-08]. （原始内容存档于2018-10-02）. 
  4. ^ Kumar, Vinay. Robbins and Coltran Pathologic Basis of Disease. China: Elsevier. 2010: 88–89. ISBN 978-1-4160-3121-5. 
  5. ^ Matsui T, Heidaran M, Miki T, Popescu N, La Rochelle W, Kraus M, Pierce J, Aaronson S. Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes. Science. 1989, 243 (4892): 800–4. PMID 2536956. doi:10.1126/science.2536956. 
  6. ^ Heidaran MA, Pierce JH, Yu JC, Lombardi D, Artrip JE, Fleming TP, Thomason A, Aaronson SA. Role of alpha beta receptor heterodimer formation in beta platelet-derived growth factor (PDGF) receptor activation by PDGF-AB. J. Biol. Chem. 25 October 1991, 266 (30): 20232–7 [2015-05-24]. PMID 1657917. （原始内容存档于2008-11-05）. 
  7. ^ Heidaran MA, Pierce JH, Jensen RA, Matsui T, Aaronson SA. Chimeric alpha- and beta-platelet-derived growth factor (PDGF) receptors define three immunoglobulin-like domains of the alpha-PDGF receptor that determine PDGF-AA binding specificity. J. Biol. Chem. 5 November 1990, 265 (31): 18741–4 [2015-05-24]. PMID 2172231. （原始内容存档于2008-07-25）. 
  8. ^ Blazevic T, Schwaiberger AV, Schreiner CE, Schachner D, Schaible AM, Grojer CS, Atanasov AG, Werz O, Dirsch VM, Heiss EH. 12/15-Lipoxygenase Contributes to Platelet-derived Growth Factor-induced Activation of Signal Transducer and Activator of Transcription 3. J. Biol. Chem. December 2013, 288 (49): 35592–603. PMC 3853304 可免费查阅. PMID 24165129. doi:10.1074/jbc.M113.489013. 
  9. ^ Yu JC, Li W, Wang LM, Uren A, Pierce JH, Heidaran MA. Differential requirement of a motif within the carboxyl-terminal domain of alpha-platelet-derived growth factor (alpha PDGF) receptor for PDGF focus forming activity chemotaxis, or growth. J. Biol. Chem. 1995, 270 (13): 7033–6. PMID 7706238. doi:10.1074/jbc.270.13.7033. 
  10. ^ Hoch RV, Soriano P. Roles of PDGF in animal development. Development. 2003, 130 (20): 4769–4784. PMID 12952899. doi:10.1242/dev.00721. 
  11. ^ Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc. Natl. Acad. Sci. U.S.A. 1996, 93 (6): 2567–2581. PMC 39839 可免费查阅. PMID 8637916. doi:10.1073/pnas.93.6.2576. 
  12. ^ Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 1996, 15 (2): 290–298. PMC 449944 可免费查阅. PMID 8617204. 
  13. ^ Maglione D, Guerriero V, Viglietto G, Ferraro MG, Aprelikova O, Alitalo K, Del Vecchio S, Lei KJ, Chou JY, Persico MG. Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14. Oncogene. 1993, 8 (4): 925–931. PMID 7681160. 
  14. ^ PDGF Pathways. [2007-11-17]. （原始内容存档于2006-11-13）. 
  15. ^ 15.0 15.1 Alvarez RH, Kantarjian HM, Cortes JE. Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin. Proc. September 2006, 81 (9): 1241–57. PMID 16970222. doi:10.4065/81.9.1241. 
  16. ^ Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J. Cell. Mol. Med. 2005, 9 (1): 59–71. PMID 15784165. doi:10.1111/j.1582-4934.2005.tb00337.x. 
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