胰島素信號(hào)轉(zhuǎn)導(dǎo)課件

胰島素信號(hào)轉(zhuǎn)導(dǎo)途徑胰島素信號(hào)轉(zhuǎn)導(dǎo)胰島素受體（InsulinReceptor，IR）結(jié)構(gòu)IR是由位于細(xì)胞外的兩個(gè)α亞基（INS特異結(jié)合部位）和位于細(xì)胞內(nèi)的兩個(gè)β亞基（信號(hào)轉(zhuǎn)導(dǎo)的重要部位）組成的四聚體。胰島素信號(hào)轉(zhuǎn)導(dǎo)INS與IR結(jié)合后，使受體上酪氨酸激酶活化TK=tyrosinekinase酪氨酸激酶胰島素信號(hào)轉(zhuǎn)導(dǎo)配體不一樣！看這里就好←←胰島素信號(hào)轉(zhuǎn)導(dǎo)IR后信號(hào)轉(zhuǎn)導(dǎo)途徑1使胰島素受體底物（InsulinReceptorSubstrate，IRS）磷酸化，變?yōu)楹琒H2結(jié)合位點(diǎn)的錨蛋白結(jié)合磷脂酰肌醇-3激酶（Phosphoinositide3-Kinase，PI3-K）胰島素信號(hào)轉(zhuǎn)導(dǎo)胰島素信號(hào)轉(zhuǎn)導(dǎo)PI3-K的P85亞基的SH2結(jié)構(gòu)域被磷酸化的IRS-1占領(lǐng)，刺激其P110亞基催化活性催化細(xì)胞質(zhì)膜上的PIP2磷酸化生成PIP3后者可與PKB/Akt的PH結(jié)構(gòu)域結(jié)合，使Akt結(jié)合在質(zhì)膜內(nèi)側(cè)面，即成為磷脂酰肌醇依賴性蛋白激酶1phosphatidy1-dependentkinase，PDK)的底物PDK激活A(yù)kt，并使Akt從膜脫落，進(jìn)入胞質(zhì)胰島素信號(hào)轉(zhuǎn)導(dǎo)胰島素信號(hào)轉(zhuǎn)導(dǎo)胰島素信號(hào)轉(zhuǎn)導(dǎo)胰島素信號(hào)轉(zhuǎn)導(dǎo)胰島素信號(hào)轉(zhuǎn)導(dǎo)IR后信號(hào)轉(zhuǎn)導(dǎo)途徑2INS與IR結(jié)合后，使受體上酪氨酸激酶活化使Shc磷酸化，變?yōu)楹琒H2結(jié)合位點(diǎn)的錨蛋白與含SH2的生長因子銜接蛋白2（Growthfactorreceptorbound2,Grb2)結(jié)合結(jié)合交換因子（Sonofsevenless,Sos)并使之活化

胰島素信號(hào)轉(zhuǎn)導(dǎo)IR后信號(hào)轉(zhuǎn)導(dǎo)途徑2活化的Ras-GTP可與一個(gè)絲氨酸/蘇氨酸蛋白激酶Raf的N端結(jié)合并使之活化它的C端再與另一個(gè)酪氨酸/蘇氨酸蛋白激酶MEK（MAP及ERK激酶）相結(jié)合，并使之活化下游及轉(zhuǎn)錄因子、RNA聚合酶II等，可以使細(xì)胞生長、增殖、分化胰島素信號(hào)轉(zhuǎn)導(dǎo)PPPPPPPPPGlycogen

Synthasec-JunEEF2KeIF4EEF2TranslationAnti-apoptosisGeneExpressionTranslationFattyAcid

SynthesisATP

CitratelyaseGlucoseEBSGene

ExpressionPPp70S6KJNKeIF4EBPInsulinDegradation

&Receptor

DephosphorylationH+eIF2BBAD14-3-3BADMEKsERKsPKCPPPPAPSc-CbIPPtase1GSK3NckIRS1SHCPPPCrkSOSGTPmTORFKHRL1LipidRaftFlotillinRasCAPGLUT4

TranslocationTREGRB10INSULINReceptor

InternalizationElkc-FosInsulin

ReceptorPIP3PIP2Akt

PKBH+EAIEAIInsulinS6RacPI3KPDKGLUT4GRB2FynlnsulinReceptorPathwayRafGLUT4

Vesiclec-CbIInsulinPSHCIRS1/2PIP2PIP3Rab4

2009C胰島素信號(hào)轉(zhuǎn)導(dǎo)參考文獻(xiàn)【1】Fr?jd?S,

VidalH,

PirolaL.Alterations

of

insulin

signaling

in

type

2

diabetes:a

review

ofthe

currentevidence

from

humans.BiochimBiophysActa.

2009Feb;1792(2):83-92.【2】RamalingamL,

OhE,

ThurmondDC.Novel

roles

for

insulinreceptor

(IR)in

adipocytes

and

skeletalmuscle

cellsvia

new

and

unexpected

substrates.CellMolLifeSci.

2013Aug;70(16):2815-2834.【3】趙海燕,王勇,馬永平等.胰島素信號(hào)轉(zhuǎn)導(dǎo)障礙與胰島素抵抗[J].新醫(yī)學(xué),20