VOi`Bnɂ鐧̋KƍזE̗\

<strong>c q</strong>
iwȊwZ^[ זEVXe`[j
emailF<a href="mailto:marikoh@rcai.riken.jp">cq</a>
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̈Zr[, <strong>3</strong>, e001 (2014)@<a href="http://dx.doi.org/10.7875/leading.author.3.e001">DOI: 10.7875/leading.author.3.e001</a>
Mariko Okada: <strong> Prediction of cellular responses based on regulatory rules of signal transduction pathways.</strong>

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<h2>v </h2>
@זẼVOi`BńC1980NC͂߂ƂaƂ̊֘Aɂ藲߂łDߔNł́C2003ÑqgQmǊƑOサĒڂт͂߂VXewɂāCƗ_Ƃ̗ZƂił镪łD̃r[ł́CזẼVOi`BñVXewIȌɑ΂҂ĂЉIъwpIȔwi͂߁CVOi`Bñ_Ci~NXƂ̔wɂ鐧̃fUCCpɂɂ݂鐧̋KCזE̐ւ̉pȂǂɂӂDΏۂƂẮCVXew̗ꂩ݂Ă܂܂Ȍ̐iłERKoHNF-BoHɂĒSɏЉDŌɁCĈ悤ȃVXew߂Đił̂C̏W]D

<h2>͂߂</h2>
@זEVOi`BńC̏]ʈqɓ`B`q̔𐧌䂷邱ƂɂזẺ^Sq@\ŁC^pÑ_CݍpCȂǐwIȔ̏ŴƂĂȂ肽Dqg̑S`q̖20VOi`BnɂƂCVOi`Bn͂ꎩ̂傫ȃlbg[NłDC̃lbg[N̓o͂̊֌W͂܂܂Ȑ̂߂ɔ`łĈ̂̃VOi𑫂Z邱ƂɂזẺ\邱Ƃ͂قƂǂłȂD̂Ƃ̓VOi`Bnُ̈Ɗ֘A̐[CCAaCǂȂǁC܂܂Ȏả𖾂юÂɂđ傫ȖłD̂悤ȔwiC1990Ň㔼CVOi`Bn̕q_Ci~NXƍזEƂɋKoƂgVXewhɂȂD̃r[ł́C15NԂɂ킽VOi`BñVXewɂ錤̓Ƃ̏ɂďЉD

<h2>1DVOi`BñVXewIȌ̔wi</h2>
@1990Ň㔼2000N̏ɂāCvȃVOi`BnłERKoHNF-BoH̃fW^ȉѐUƂ̋@Ɋւ錤\ꂽ<a href="#R1"><sup>1,2)</sup></a>D̘_ɂCVOi`Bn͂܂ōlĂȏɃ_Ci~NXɕx񂾌nłCɂ͂܂炩ɂĂȂq̂Ă邱ƂꂽDɂ̂CqgQmǂꂽD@ɁCQmƂɂnCX[vbgȉ͋Zp₻T|[gc[[C炪I~NX͂𒆐SƂgbv_E^̌CсC^[Qbgڂăf\zĉ͂{gAbv^̌2̃^CṽVXew̌Dgbv_E^̌ɂẮCɂK͂ÓIȕqԑݍp̃lbg[NЉIȃlbg[NƗގ\Ƃ炩ɂCɕpolbg[N`[t𓯒肷邱Ƃɂ萶̃lbg[N̕ՐwEꂽ<a href="#R3"><sup>3,4)</sup></a>D܂C{gAbv^̌ɂẮCHwCӍHwCw̉eIȃf\zCVOi̓Ԃ肷镪q䂪\ꂽ<a href="#R5"><sup>5,6)</sup></a>D̂悤ɂāC܂܂Ȏf[^𗝘_Iɐ邽߁C邢́CVXeƂė邽߁CVXewL܂Ăi<a href="#F1">}1</a>jD

<a name="F1"></a><div id="fig1-caption-text" style="display: none;"><strong>}1@VXew̃Av[`</strong>
ЂƂɃVXewƂĂC邢͗_Cgbv_E^邢̓{gAbv^ȂǁC܂܂ȕ@_Av[`D2000N㏉ɂ͂̌͌ʂɍsĂC̖10Ň݁C炳܂܂ȃAv[`͗ZxɂȂĂD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/12/Okada-3.e001-Fig.1.jpg" target="_blank">[Download]</a></div>[hs_figure id=1&amp;image=/wordpress/wp-content/uploads/2013/12/Okada-3.e001-Fig.1.png&amp;caption=fig1-caption-text]

@זEVOi`BñVXewIȌ̖ړÎЂƂ́CGȃVOĩlbg[NזẺg\h邱ƂłD̔wiɂ́C1990N㔼ŝ悤ɂȂqWICƂ΁CEGFiErbB1jê̕WI܂łQtB`juixΏۂƂjCBcr-Abl̕WI܂łC}`juiaΏۂƂjCErbB2̕WI܂łgXcY}uiΏۂƂjCȂǂ̓oꂪ<a href="#R7"><sup>7)</sup></a>DQtB`juуgXcY}u͖êłErbBt@~[WIƂ邪CErbBt@~[͊ɂƂȂzʑ̂邢̓weʑ̂`邱ƂCƂ΁CErbB11̕WIƂĂזEɂċقErbBt@~[ԐړIɑjQĂ܂DCǂꂾ̐xĂCזEɂErbB1ƂقErbBt@~[ɑ΂܂̌ʂ̈ႢʓIɐ؂蕪邱Ƃ͍łD܂CQtB`ju邢̓gXcY}u̓^ɂErbBt@~[𒷊Ԃɂ킽jQƁCق̎ê̌oHoRErbBt@~[̉̌oHƂܑϐ̖Ă<a href="#R8"><sup>8)</sup></a>DƂC܂̎ʂѕʂ̉eʓIɕ]C琶邩Ȃp܊J̑iK\邱Ƃ҂悤ɂȂD̖܂JƂł͑琔fpVOi`Bn̗_IȌsĂCƘAgO[vC܂Chx`[Ƃł́CVOi`BnΏۂƂK͂ȃf̍\z<a href="#R9"><sup>9)</sup></a>C𗘗p䕪q܌ʂ̗\C܂CI~NXf[^瓝vIȎ@pălbg[N\s<a href="#R10"><sup>10)</sup></a>CזE^̌q𓯒肵ĂD

<h2>2DVOiِ̓ƔF</h2>
@זEVOi`BñVXewIȌ̂ЂƂ̖ړÍCVOi`Bnِ̓уVOi`B̕q@\̉𖾂łDƂ̂CêƃKhƂ̓ٓIȌƁCVOi`Bnɂ^pNِ͔̔rIႭCVOi`Bnِ̓єFǂ̂͂܂悭킩ĂȂłDƂ΁CyfɂĂ͌ƌ̂悤ȍyfƊƂ̗̍\̔FɊւ闝_Cyfِ̓\킷p[^[Ȃǂ琶̗ʂx͗\邱ƂłDCVOi`B̃lbg[Nِ̓́CɊ܂܂yfCƂ΁CveCLi[[ِ̓Ƃď\ɂ͐łȂDȂȂCveCLi[[͊̂ЂƂłATPɑ΂錋ِ͍C^pN̊ɑ΂ِ͈ʓIɒႢł<a href="#R11"><sup>11)</sup></a>D̂Ƃ́CSH2hCƃ`V_^pNƂ̂̂悤ȕqԑݍpɂĂł<a href="#R12"><sup>12)</sup></a>D̂悤ȕqFِ̓̒Ⴓ̓VOi`B̃lbg[Nɏ璷iredundancyjъ拭irobustnessjC`qɕψق⌇Ȃǂُ̈킪NĂlbg[NŜ̋@\ێłƂ_ŐɂƂ藘_łDŁCVOi`B݂̑̈ӖƂ́Ĉ悤ȏ璷̂Ȃ̏I蕪Ċjɂē̓]ʈq邱Ƃɂ͂łD̋@\𖾂炩ɂ邱Ƃł΁ĈƂזE̗\ɗpCɂ́Cp̂ȂזE̐䂪\ɂȂ͂łD
@̏璷ѓِƂ킹VOi`Bn̊Ղ̂ЂƂ́CVOi^pÑ}`hC<a href="#R13"><sup>13)</sup></a>iW[jCсC^pN̂ʂ𒼐ڂɐ䂷̂ł͂ȂC痣ꂽ䕔ʂCC^pN̗̍\ω邱Ƃɂ芈u䂷ƂAXebN<a href="#R11"><sup>11)</sup></a> łD}`hC͂ЂƂ̃VOi^pNɕ̃^pNƂ̑ݍp\ɂCƂ΁CA_v^[^pNłGab2CGrb2CShcSH2hC邢PTBhCČ݂ɖêƌCǂ̃A_v^[^pNoRĂERKoHł悤ȏ璷ȃlbg[N`i<a href="#F2">}2a</a>jD܂lɁC̃VOi^pNɂ̓_ȂǃAXebNȐ䂪C̃tB[hobN邢͕̃tB[hobN̍p_ƂĂ͂炢CVOi^pN̋Ǎݐω肷D̂ȂŁC̃AXebN̓VOi^pN̂̋߁C`ȏóCȂ킿CٓIȊЂoi<a href="#F2">}2b</a>jD

<a name="F2"></a><div id="fig2-caption-text" style="display: none;"><strong>}2@VOȉ璷Ɠِ</strong>
iajVOi^pÑW[\DVOi`B̏璷Ƌ̓VOi^pÑ}`hCɗRD
ibjlbg[N`[tƃVOi^pN̋ǍݐD1FPȕqԑݍp͐`o͊֌WC2F̃tB[hobNC邢́C3F^pNƁC`ȉD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/12/Okada-3.e001-Fig.2.jpg" target="_blank">[Download]</a></div>[hs_figure id=2&amp;image=/wordpress/wp-content/uploads/2013/12/Okada-3.e001-Fig.2.png&amp;caption=fig2-caption-text]


<h2>3DזẼfW^ȉ</h2>
@VOi`Bn̖ڂ̂ЂƂ̓AiOȃVOĩfW^ւ̕ϊłD́CقȂʂ10̏ʂɕς@\łDƂ΁CKhƎêƂ̔x́CVOiŜ̋xƓ]ʂɂo͂ɑ傫eD̓͂̈Ⴂ́CqR̂ȂǈقȂ郊KhƂƂ邵CKhłĂZxقȂꍇD̂悤ȈႢɂ́CKh̐ea邢͎ê̔ʂ傫eDC̐ea邢͔ʂ̈ႢƂ́C܂łl̑召̈ႢiAiÖႢjłDƂ낪CԂɂĐ琔\̃VOi`Bn̔ւƁC̃AiOȃVOiʂ̈ႢC01̃fW^ȓ]ʊ̈ႢƂČꍇD̂悤ȓ]ʂɂo͂̃fW^ւ̕ϊ͍זẼVOi`Bn̂@\̂ЂƂłCזEIɕς邱Ƃ̂ł\D܂ł̗_IȌɂC̃tB[hobN<a href="#R1"><sup>1,14)</sup></a>CݑjQ<a href="#R15"><sup>15)</sup></a>ĈɏqׂANDQ[g<a href="#R16"><sup>16)</sup></a>Ĉ悤ȃlbg[N`[tזẼfW^Ȋ𐶂邱ƂĂi<a href="#F3">}3</a>jDɁĈ悤Ȗ炩ȃlbg[N`[tȂꍇłCƂ΁CERK̕zIȓd_̏ꍇɂ́C2̃_E_yf̗ʂȂ悤ȓʂȃp^[^[̏ɂČn͎IȑݑjQƂĂ͂炫CfW^ȏo͂悤ɂȂ<a href="#R17"><sup>17)</sup></a>Dlbg[NƓԂƂ̊֌WɂẮCɏqׂERKoHƂ悭ĂD

<a name="F3"></a><div id="fig3-caption-text" style="display: none;"><strong>}3@fW^ȉUN邱Ƃ̂łlbg[N̍\</strong>
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/12/Okada-3.e001-Fig.3.jpg" target="_blank">[Download]</a></div>[hs_figure id=3&amp;image=/wordpress/wp-content/uploads/2013/12/Okada-3.e001-Fig.3.png&amp;caption=fig3-caption-text]


<h2>4DERKoH̓</h2>
@ERḰCEGFéCPDGFéCCXéCIGFéCFGFéCTrkêȂǁC܂܂ȖễVOiW񂷂Z/XIjLi[[łCזȆBCCȂǁC܂܂ȍזE̐ɂ<a href="#R18"><sup>18)</sup></a>DERKRas-Raf-MEK-ERKoHւĊCƍזEjւƈڍsCELK邢CREBȂǂ̓]ʈq`q̔UDERKoHł́CɏqׂC̃tB[hobN<a href="#R14"><sup>14)</sup></a>CݑjQ<a href="#R17"><sup>17)</sup></a>CANDQ[g<a href="#R16"><sup>16)</sup></a> ́CfW^𐶂邷ׂẴlbg[N`[t񍐂ĂDɁC̊̓ԂƂĂCߐ̊邢͎̊̂قC̐U񍐂Ă<a href="#R19"><sup>19,20)</sup></a>i<a href="#F4">}4</a>jD̂悤Ȃ܂܂Ȕ̓͗_z肳Raf-MEK-ERKoHɂd_̔lidistributive邢processivej̈Ⴂɂ傫ȉeDERKoHɂfW^ȏo͂ƂẮCERK̂̂̃fW^ȊCсCERKɂ]ʈqc-Fos̃fW^ւ̕ϊ񍐂ĂD2̃P[Xł͂ǂERK̎IȊKvŁCERK̎ERKRafւ̐̃tB[hobN<a href="#R14"><sup>14)</sup></a>Cê̊̋<a href="#R21"><sup>21)</sup></a>CRas邢Rap1̊LleBNXɂ鑊IȌ<a href="#R22"><sup>22)</sup></a> ȂǂɗR邱Ƃ񍐂ĂCזE邢̓KhƂɌ肳ĂƍlD

<a name="F4"></a><div id="fig4-caption-text" style="display: none;"><strong>}4@ERKoH̓VXewɂĂƂĂnł</strong>
ԃ_Ci~NXїpʉɂ͂ƂɁC܂܂ȃ_Ci~NX񍐂ĂD܂C̃_Ci~NX𐶂ޗ_Iȍ񏥂ĂD̃p[^[̂ƁC̃tB[hobN͎Iiԃ_Ci~NXjCClIipʉjȉD܂C̃tB[hobN͈ߐ̉UƂDƃ_Ci~NXƂ̊֘ÁCERK݂̂Ȃ炸Cق̃VOi`Bn邢͓]ʈq̊ɂĂʂ_D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/12/Okada-3.e001-Fig.4.jpg" target="_blank">[Download]</a></div>[hs_figure id=4&amp;image=/wordpress/wp-content/uploads/2013/12/Okada-3.e001-Fig.4.png&amp;caption=fig4-caption-text]

@ERK̎IȊ͍זE̐ɑ傫ȉeDƂ悭Ă郉bg̕tɗRPC12זE<a href="#R14"><sup>14,22)</sup></a> qg̓ɗRMCF-7זE<a href="#R23"><sup>23)</sup></a> ɂẮCߓIERK̊ł͍זEBCIERK̊ł͍זECƂقȂ\^Ƃ킩ĂDقȂ\^Uł闝R̂ЂƂ́CזE̐̏̒iKɂāCIERK݂̊̂CERK̂ɂ`q̗Uꂽ]ʈqł邱ƂɗRƍlDc-Fos邢c-MycȂǂ̓]ʈqERKɈˑIȑ`qƂăR[hCCDEFhCƂERKZT[z<a href="#R24"><sup>24)</sup></a>DDEFhC^pNERKɂ艻邪CŁCmRNAƂERK̊łɗ}Ăꍇɂ͂̃^pN݂͂₩ɕDāCERK̊Iȏꍇɂ̂݁C̈`q̓^pNƂĔDê̊ɂc-<em>fos</em> mRNA̔ɂ͖30Cc-Fos^pN̔ɂ͖60`90邽߁C̈`q^pNƂĔ邽߂ɂ90ȏ̎ERK̊KvƂȂD̃lbg[Nł͓ERK̊łߐ̊͂̃mCYƍlC]ʂɂ̓VOiƂē`BȂDāCc-Fos̔̒iK01̃fW^ȏo͂<a href="#R25"><sup>25)</sup></a>D
@c-Fos̔̂߂ɂ́Cjɑ݂ERKɂc-<em>fos</em> mRNA̔ƁCזEɂ鎝IERK̊ɂc-Fos̈艻2̏KvłD̕qlbg[ŃCɏqׂANDQ[gƂlbg[N`[tŕ\킳<a href="#R16"><sup>16)</sup></a>DANDQ[ǵC2̓͂Ƃ̂1̃VOio͂Cǂ炩̓́C邢́Cǂ̓͂Ȃꍇɂ0̃VOio͂_HŁCVOȋI蕪sĂD낢ƂɁČoHł͍זEɂERK̊IłĂCjɂERK̊͒E_yfɂ葁XɕsߐƂȂD̂ƂɂCc-<em>fos</em> mRNA͈̔ߐƂȂDזEƊjɂERK̊̎̈Ⴂc-Fos̃fW^ȏo͂܂ԓɐC]ʈqc-Fosɂ`qɐ䂵Ă邱ƂD

<h2>5DNF-BoH̓</h2>
@ERKoHƓlɁCNF-BoH܂fW^Ȋ𐶂@\Ƃ킩ĂDNF-B͉ǂ₪ȂǂɂVOi`BnɂăVOiW񂷂]ʈqłCƉuזE̕ɂĂdvȖ͂ĂDNF-BoHɂ́CTNFȂǂ̉ǐTCgJC邢͍Rêɂ芈p50CRelACc-RelɈˑIȌÓTIȌoHicanonical pathwayjƁCBAFF邢CD40Lɂ芈p52RelBɈˑIȔÓTIȌoHinon-canonical pathwayj2<a href="#R26"><sup>26,27)</sup></a>D̂CÓTIȌoH͂̃_Ci~NXrI悭ĂDTNFȂǂ̎hɂCNF-B̑jQ^pNłIBVOiɈˑIɕ邱ƂɂNF-BCNF-B͍זEjւƈڍs`q̔UDC̑`qɃR[h^pNɂNF-B̑jQ^pNłIBA20܂܂Ă̂ŁCꂽNF-B͂̃^pNɂӂёjQCזEɎhĂ60̂ɂ͕sȏԂɂǂD̂悤Ȑƕ̔ɂNF-B͍זEƊjƂsUU邱ƁCIB̃AC\tH[̂ł̐Uɑ΂ʂ̈قȂ邱ƂoĂ<a href="#R2"><sup>2)</sup></a>D̂ƂCEFX^ubg@ȂǂpĒׂזȄWcŜɂNF-B̊́CזEɂh̔Zx̏㏸ɂƂȂ񂾂Ə㏸AiOȂ̂ɂ݂D̂̂C1זEC[WO@ɂ͂ɂCh̗ʂƐUזĚƂ01̃fW^Ȋł邱Ƃ炩ɂȂ<a href="#R28"><sup>28,29)</sup></a>Ďۂ̔wiɂ́CNF-B̗̊L肷臒l肷@\݂̑lĂDCؖK؂ȃ|[^[AbZCnȂȂǂ̗RɂCǂVOi`B̐@\͂܂܂Ŗ炩ɂĂȂD
@ŋ߁CM҂́CNF-B̊臒l肷@\݂̑Ƃ̐̎̂𖾂炩ɂ邽߁CBזEễVOi`BnɂCARMA1-TAK1-IKKoHɒڂC̃^pN̊̓ԂNF-B̊Ƃ̊֌WVXewIɉ͂DBזEê̊ɂCveCLi[[CɂCARMA1Ser668_CARMA1͑^pNƂċ@\CTAK1Ȃǂƕ̂`ĂCIKK̊𑣐iD̂ƂCIKKCARMA1Ser578̃_̃tB[hobN͂炫CIKK̊葝邱Ƃ񍐂Ă<a href="#R30"><sup>30)</sup></a>DʓIɁC̃tB[hobNERK̏ꍇ̂悤ɃVOi̊邪CƂƂāCfW^ȉ𐶂邱ƂłDgBזEDT40pʓIȎ̌ʁC̐̃tB[hobNTAK1̊̎ԂL΂CɁCIKKNF-B̃IIt𓱂Ƃ炩ɂȂDɁC̐͂ł́CIKKƂIKKIS}[̋IȊdvłƂꂽDŋ߂̌ł͂̉𗠂Â悤ɁC^pN̗̍\͂̌ʂIKK̂̂̌̕`̊̐ɏdvł邱Ƃ񍐂Ă<a href="#R31"><sup>31)</sup></a>CIKK̂̋IȊ̋@\NF-B̃VOĩfW^ȏo͂ɑ傫֗^ƍlD̂Ƃ́CIKKPNF-B̏㗬ɂƂłȂCn̂ȂŏdvȖ͂ĂƂ܂ł̒mƂvĂD

<h2>6DVOi`Bnɂ镉̃tB[hobN</h2>
@܂łɁC̃tB[hobNɂЂN镪q_Ci~NX̌ȕωɂĉĂC̃tB[hobN̕񍐂͂ނ둽͂ȂDŁC̃tB[hobN̓VOi`Bnɂ͕KƂĂقǂ悭݂Dɂ́CGabCShcCCrkȂǃA_v^[^pÑ̕_ɂ́C܂CDUSPiERKWIjCA20iIKKWIjCIBiNF-BWIjCSocs3iSTAT3WIjCMig6iEGFRWIjȂǂ̓]ʎYVOǐȂǂ񍐂Ă<a href="#R32"><sup>32)</sup></a>D̃tB[hobN̓VOi̒~ɂ킦C`ȏo͂`ɂCn̑ŜɕۂCmCY肷D~邱ƂC̃tB[hobN͒PȈߐ̃s[NƂD̂ȂŁČ҂̋ЂĂ̂̓VOi̐UłD
@זETY̐ÚCNF-BoH̗ɂĉ̃tB[hobNɂ킦C̃tB[hobNɂ`Ă<a href="#R33"><sup>33)</sup></a>DERKVOiNF-BVOiɂĂU񍐂Ă<a href="#R20"><sup>20,28,29,34)</sup></a>DCזETŶ悤ɐÜӖmȌnƂ͈قȂC̃VOi̐UזE̋@\ƂĕKvȂ̂ǂƂ_ɂĂ͂܂mȓ͓ĂȂDƂɁCERKVOi̐U͍זEẍႢp[^[̈ႢȂǂ̏̂Ƃł݂Ȃ̂ɑ΂<a href="#R20"><sup>20,34)</sup></a>CNF-BVOi̐U̓KhقȂĂזEقȂĂČ悭ώ@D̂悤ɍČ̍̏ꍇC𐶂@\ы@\͂łD݁CNF-BVOi̐ÜӋ`ƂẮC̐Ủ񐔂`q̋x߂<a href="#R29"><sup>29)</sup></a>C邢́CUƂ̃Gh|Cg̊dvłCƂDۂɁCNF-B̌҂̑́CNF-BVOi̐Uɂ̃}߂Ă悤ȂƂ낪D
@̐ÜӋ`ɊւĂ͍̌ɂ薾炩ɂĂł낤C񉽂̈Ӗ̂킩ȂU̐IȈӋ`Ƃɂ蓾闘_́CU𐶂鐧݂̂VȍזE̐̕@Ƃėp邱Ƃł邱ƂłDʓIɁĈ悤ȓIȕq_Ci~NX͂𐶂lbg[N`[t݂ĂDč𒆐Sɋ}ɐi߂Ă鍇ẃCVOi`Bñlbg[N`[tgݍ킹ClHIɍ\זE𑀍삵悤Ƃ̂łD̂ƂȂ錤ł́CL̃VOi^pN𗘗py̍זE]ȂǂɐĂ<a href="#R35"><sup>35,36)</sup></a>D

<h2>7DזEɂǍ݂ƕq_Ci~NX</h2>
@ERKoH邢NF-BoH̃lbg[N̍\͕q_Ci~NXɑ傫ȉe邪CזEɂ镪q̋Ǎ݂܂C_Ci~NX̌`ɏdvȖ͂DזEɂǍ݂͕q̔ZxǏIɍ߁Cq̂̔̌CVOĩIItЂo肷ʂDƂ΁CPHhCA_v^[^pNPI3K̊ɂזEɐPIP3ɌċǍ݂C̑\łGabIRSPI3KCRasGAPCSHP2Ȃǂ̃^pNЂ邱Ƃɂ肱̂̔̌DGabIRSȂǂ̃A_v^[^pN̓VOi̖̊ƂƂɁCVOi㏸ꍇɂ͕̃tB[hobNăVOi~SD̃VOĩIIt݂̂͐fɂ薾mɐĂ<a href="#R37"><sup>37)</sup></a>D
@܂CNF-BoHɂCARMA1 <a href="#R38"><sup>38)</sup></a> ERKoHɂKSR <a href="#R35"><sup>35)</sup></a> ́CꂼTAK-IKKoHRaf-MEK-ERKoHȂǂ̃Li[[̑^pNƂĂ͂炫C̃^pNWăJXP[hِ̓ьCVOĩXCb`ЂN肷<a href="#R39"><sup>39)</sup></a>DC̔̏㏸XCb`͑^pNƂƌLi[[Ƃ̔䗦ɑ傫ˑC̔䗦KłȂꍇɂ͋tɃLi[[̌邱Ƃ<a href="#R40"><sup>40)</sup></a>D܂CɏqׂNF-BoH̗ɂ悤ɁCזEƊjƂقȂRp[gĝ̈ڍs܂Cِ̓̏㏸ɍvD̂悤ȍזEɂǍݐ̋[ƂāCŋ߁C񍐂ꂽזEɊ֘A^pN̍זEƊĵ̈ڍsƐ̃tB[hobNƂ̘A<a href="#R41"><sup>41)</sup></a>Dł́CȂזE͕stȂ̂ƂƂɒڂĈƂVXewIɏؖꂽDȂ킿CԊ番ɂזEɂCdk1-Cyclin B1͍̂זEjւƈڍs邪ĈƂCCyclin B1̃_čזECdk1-Cyclin B1̂ɊjւƎ荞ސ̃tB[hobN䂪͂炭Ƃ킩D̐̃tB[hobN̍ɂCqXeVXi킦͂ŏ̏Ԃ̂ƂƓɂĂCԂ͊Sɂ͂ǂȂƁjƂ̕stזEɓ˓̂łD̂悤ɁCזE̓Ԃ邢̓lbg[Nł͂ȂCזEɂǍ݂܂Cِ̓̔ɑ傫v邱ƂXɂ킩ĂĂD

<h2>8D{gAbvgbv_E</h2>
@܂ŏqׂĂ悤ɁC{gAbv^̃fÕAv[`́C܂܂Ȑ̋@\𖾂炩ɂ邱ƂɂCזE̐̋@\ɂ͈̋K̂邱ƂĂDC̃fǑɂ͑̎OmKvłDŁCߔÑI~NXZp̔WɂCgXNvg[CveI[C^{[CGsWFleBNXȂǂ̉͂rIeՂɍs悤ɂȂC̃gbv_E^̌ƃ{gAbv^̌ƂZĈȂԂ番q̋@\肵CזĚ`肷镪q}[J[o肵悤ƂĂDƂƁCgbv_E^̃I~NX͕čɂĂŁC{gAbv^̃fO͉BɂĂƂXCŋ߂ł́CBɂĂI~NXLs悤ɂȂC̕@_͕̓WɂȂD݁Ĉ悤Ȍ͂܂܂ȂΏۂƂĂ邪Cŋ߂ł́CƉuwȂǂ̂ق̕ɂĂI~NXƃfOƂ킹ĂĂD䐫TזEɂgXNvg[̃f[^]ʈqFoxp3̃lbg[ÑfW^ȐfOɂ蓯肵̂́ĈЂƂł<a href="#R42"><sup>42)</sup></a>D
@CI~NXƃfOƂ̓͂̂́CQmCh֘Áigenome-wide association studyFGWASjȂǃQmRz[g<a href="#R43"><sup>43)</sup></a> Ƃ̗Zł낤i<a href="#F5">}5</a>jDƂ΁C鎾a̔ǂ̗LC邢́CǂƂ̎́Celő傫قȂDǂ̗L͊elɂƂĂ01̃fW^ȉƓ`łD܂Cǂ鎞͈`qłȂ̉eɂ傫قȂ邪ĈƂ͂̃p[^[ɑ΂lƂ̈ႢƂĂƂ炦邱Ƃł邾낤D͂߂Ƃqg̑K̓Qm͂̌ʂC̈`qُ̈́CPIK3CACPIK3R1CPTENCAKT1CMAP3K1CKRASCBRAFCEGFRȂǂEGFê邢ErbB̂閌ễVOi`Bnɋɒ[ɂĂ邱Ƃ񍐂Ă<a href="#R44"><sup>44)</sup></a>DĈ̂̊҂̃xɂĂǂ̂悤Ȉ`qُ̑ĝC܂Cُ̈xƗ\Ƃ̊֌WȂǂɂĂ͂܂炩ɂĂȂD̂悤ȓ͂Əo͂Ƃ̊֌W̗\̓lbg[ÑfOɂ\ɂȂ邩ȂDƂ΁C`q̑̓^pN̏̔Zx̏㏸C^pN̕ψق͕qԑݍpyf-Ԃ̌ea̕ωȂǂ̃p[^[Ƃĕ\킷ƂłDɁCɂق̈`q̑ݍptB[hobNȂǂ̃lbg[N\ƁC̃xł̔ǂ͔`ɂȂ͂łD̂悤Ȍnł́C1`q̂킸Ȕʂ̈Ⴂ^pN̂̐eäႢC̂̂̌IȈႢ𐶂݂Ă͂ȂD܂ŁClƂɐKȂǂςĈ`q̊̃p[^[𐧌䂵ǂ𖢑RɖhƂCʉ\hŵ悤ȂƂ\ɂȂ̂ł͂ȂƑzĂD

<a name="F5"></a><div id="fig5-caption-text" style="display: none;"><strong>}5@{gAbvgbv_E</strong>
ꂩ̃VXewނ́Ćg\́hɂƂÂCqǧNΏۂƂ\hwƐ؂藣ȂDqg̑SQmpV~[VƎa̔ǋ@\̗ɉpł낤D܂Clbg[N`[t̍זȆւ̉ppł낤D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/12/Okada-3.e001-Fig.5.jpg" target="_blank">[Download]</a></div>[hs_figure id=5&amp;image=/wordpress/wp-content/uploads/2013/12/Okada-3.e001-Fig.5.png&amp;caption=fig5-caption-text]


<h2></h2>
@̃r[ł́CqgQm̌ƘAĔWVOi`BñVXewIȌɂāC15NԂ̓삯ŐDM҂𒆐SɌi߂Ă邱Ƃn̐ʂɂƂ肠Cł͐Ȃ_IȌ<a href="#R45"><sup>45-48)</sup></a>DŏЉlbg[N̗_́CVOi`BnłȂ]ʈq邢͍זEԂ̐ɂpłėp̍lłD2012NC<em>Mycoplasma</em>ۂ̑SזEf\<a href="#R49"><sup>49)</sup></a>C傫ȘbɂȂD܂C1׋ۂ̃fł͂DĈƂɐGꂽ̃O[v́ĈɃqg̑SQmf݂Ă̂͂܂Ȃ낤DẴVXew̌̌ł͂łɗՏ҂Ƃ̘Ag}ɐiłC܂̎_ł͂肦ȂƎvȂCqgQmɂƂÂ̔Ǘ\f\Ȃ悤ȋCĂDCK̓f\zۂɁCRƑ傫ȃf\ẑł͂ȂCȂ炩̗_ɂƂÂf\zق\xƂC܂܂ł̃VOi`B̃fǑ̌ʂĂDɂĂCVXew݂̋́g\hłD̎҂fV~[VЂƂ̎c[ƍl悤CC킪ɂĂ܂܂Ȍ̘Ag̐iނƂ]܂D

<h2> </h2>
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<h2>Ql}</h2>
<ol>
<span class='au'>]m</span>: <span class="ti">זẼVXew.</span> <span class='so'>o (2008)</span>
</ol>
<ol>
<span class='au'>Uri Alon (), qcV, {  ()</span>: <span class="ti">VXew: H̐݌v.</span> <span class='so'>o (2008)</span>
</ol>
<ol>
<span class='au'>Alberts, B., Johnson, A., Lewis, J. et al</span>: <span class="ti">Molecular Biology of the Cell, 5th Ed, Chapter 7 & Chapter 15.</span> <span class='so'>Garland Science, New York (2008)</span>
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<ol>
<span class='au'>Voit, E. O</span>: <span class="ti">A First Course in Systems Biology.</span> <span class='so'>Garland Science, New York (2012)</span>
</ol>
<ol>
<span class="ti">Uri Alonfs Systems Biology Lecture-YouTube.</span> <span class='so'><a href="http://www.youtube.com/watch?v=Z__BHVFP0Lk" target="_blank">http://www.youtube.com/watch?v=Z__BHVFP0Lk</a></span>
</ol>
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