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== Mecanismos ==
TheO [[Receptor (biochemistrybioquímica)|receptor]] fordo PDGF, é o '''PDGFR''', isque classifiedse asclasifica acomo un [[receptor tyrosinetirosina kinasequinase]] (RTK), aun typetipo ofde [[plasmareceptor membrane|cellda superficie surfacecelular]] receptor. Identificáronse Twodous typestipos ofde PDGFRsPDGFR: haveos beenPDGFR identified:de alpha-typetipo andalfa beta-typee PDGFRsde tipo beta.<ref>{{cite journal |vauthors=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> TheO alphatipo typealfa bindsúnese toao PDGF-AA, PDGF-BB ande PDGF-AB, whereasmentres theque beta typeo PDGFR bindsde withtipo highbeta affinityúnese tocon alta afinidade a PDGF-BB ande PDGF-AB.<ref>{{cite journal |vauthors=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>
O PDGF bindsúnese toao thepeto PDGFRde ligandunión bindingao pocketligando locatedde withinPDGFR thelocalizado secondno andsegundo thirde immunoglobulinteerceiro domains[[dominio de inmunoglobulina|dominios de inmunoglobulina]].<ref>{{cite journal |vauthors=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> UponDespois activationde bysern activados polo PDGF, theseestes receptorsreceptores dimerisedimerízanse, ande areson "switched onencendidos" bypor auto-[[phosphorylationfosforilación]] ofde severalvarios sitessitios onnos theirseus dominios [[cytosolcitosol|citosólicos]]ic domains, whichque serveserven topara mediatemediar bindinga ofunión cofactorsde andcofactores subsequentlye activateactivar seguidaemtne a [[signaltransdución de transductionsinais]], forpor exampleexemplo, throughpola thevía da [[Phosphoinositidefosfoinosítido 3-kinasequinase|PI3K]] pathwayou orpola throughactivación mediada por [[reactiveespecies oxygenreactivas speciesdo (ROS)oxíxeno]]-mediated activationda of thevía [[STAT3]] pathway.<ref name="pmid24165129">{{cite journal |vauthors=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> DownstreamOs effectsefectos of[[augas thisabaixo]] includedisto regulationinclúen ofa regulación da [[geneexpresión expressionxénica]] ande theo [[cellciclo cyclecelular]].
TheO rolepapel ofde PI3K hasfoi beeninvestigado investigatedpor byvarios several laboratorieslaboratorios. AccumulatingOs datadatros suggestsacumulados thatsuxiren que, whileaínda thisque moleculeesta ismolécula é, inen generalxeral, partparte ofco growthcomplexo signalingde complexsinalización de crecemento, itxoga playsun apapel moremáis profoundprofundo roleen incontrolar controllinga cellmigración migrationcelular.<ref>{{cite journal |vauthors=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>
As diferentes isoformas do ligando teñen afinidades variables para as isoformas do receptor, e as isoformas do receptor poden variablemente formar hetero- ou homodímeros. Isto orixina a especificidade da sinalización augas abaixo. Demostrouse que o [[oncoxene sis]] deriva do [[xene]] da cadea B do PDGF. O PDGF-BB é o ligando de maior afinidade para o PDGFR-beta; o PDGFR-beta é un marcador da activación de células esteladas hepáticas no proceso da [[fibroxénese]].<ref>Peri Kocabayoglu, Abigale Lade, Youngmin A. Lee, Ana-Cristina Dragomir, Xiaochen Sun, M. Isabel Fiel, Swan Thung, Costica Aloman, Philippe Soriano, Yujin Hoshida, e Scott L. Friedman. β-PDGF Receptor Expressed by Hepatic Stellate Cells Regulates Fibrosis in Murine Liver Injury, but Not Carcinogenesis. J Hepatol. 2015 Jul; 63(1): 141–147. Published online 2015 Feb 9. doi: 10.1016/j.jhep.2015.01.036. PMID: 25678385</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}}
== Función ==
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>{{cite journal|last1=Ataliotis|first1=P|last2=Symes|first2=K|last3=Chou|first3=MM|last4=Ho|first4=L|last5=Mercola|first5=M|title=PDGF signalling is required for gastrulation of Xenopus laevis.|journal=Development|date=September 1995|volume=121|issue=9|pages=3099–110|pmid=7555734}}</ref><ref>{{cite journal|last1=Symes|first1=K|last2=Mercola|first2=M|title=Embryonic mesoderm cells spread in response to platelet-derived growth factor and signaling by phosphatidylinositol 3-kinase.|journal=Proceedings of the National Academy of Sciences of the United States of America|date=3 September 1996|volume=93|issue=18|pages=9641–4|pmid=8790383|doi=10.1073/pnas.93.18.9641|pmc=38481}}</ref><ref name="PUB00014075">{{cite journal |vauthors=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 |vauthors=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 |vauthors=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 |vauthors=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>
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