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* 호르몬과 표적기관

* 호르몬과 표적기관. calcitonin : C 세포에서 분비 Ca 저하. Physiological information cascade. GHRH(GH) GnRH(CH,FSH) TRH(TSH) CRH(ACTH). GHIH PRIH.   . T 3 /T 4. 뼈에서 유리 신장 재흡수. glucocorticoid aldosterone. * Cellular signal transduction. Tf 인산화. < 세포의 자극에 의한 유전자 발현 조절 >.

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* 호르몬과 표적기관

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  1. * 호르몬과 표적기관 calcitonin : C세포에서 분비 Ca저하 Physiological information cascade GHRH(GH) GnRH(CH,FSH) TRH(TSH) CRH(ACTH) GHIH PRIH    T3/T4 뼈에서 유리 신장 재흡수 glucocorticoid aldosterone

  2. * Cellular signal transduction Tf 인산화 <세포의 자극에 의한 유전자 발현 조절>

  3. Signal Transduction • Hormones, growth factors, stresses등과 같은 많은 세포외적 자극을 수용하여 이러한 자극들을 인지하고 세포 내로 전달하여야 한다. 이러한 일련의 과정을 signal transduction이라고 한다.

  4. Intracellular Receptor • Steroid hormone • Carrier에 의해 표적세포까지 이동 carrier 해리 단순수송 intracellular receptor 핵공 통과 DNA 결합 전사조절

  5. Cell Surface Receptor • Hydrophilic molecule • Cell surface receptor mediate signaling • Ion channel-linked receptor; transmitter-gated ion channel • G-protein-linked receptor ; cAMP pathway, Ca2+ pathway • Enzyme-linked receptor; cytoplasmic domain functions as an enzyme

  6. G protein coupled Receptor • Seven-folded membrane protein • 신호분자의 결합으로 trimeric GTP-binding protein 활성화 • Trimeric G-protein의 작동양식 • 구성 ; α chain ; GTP 결합, 분해 β/γ ; tight complex, γ의 prenyl group 매개로 부착 • G trimer - GDP GTP  βγ해리α의 활성화, βγ도, target protein과 상호작용

  7. Protein Kinase A (cAMP) CREB: CRE binding protein

  8. Protein Kinase C (Ca2+) Phospholipase C는원형질막의 phosphatidylinositol 2-phosphate(PIP2)를 diacylglycerol(DAG)와 inositoltriphosphate(IP3)로 분해한다 • Serine/threonine protein kinase (PKC) 활성화; Ca2+의존성 (세포질세포막) • IP3는 세포질로 이동한 후 소포체의 외막에 있는 칼슘통로에 결합하여 이들을 열리게 한다. 칼슘이온이 세포질로 이동하여 칼슘농도를 증가시킨다

  9. Receptor Tyrosine Kinase • Receptor tyrosine kinases (TKs or RTKs) phosphorylate specific tyrosines on a small set of intracellular signaling proteins. EGF, VEGF, M-CSF PDGF, HGF, IGF-1 FGF, NGF Insulin • ligand binding에 의한 dimerization  autophosphorylation • 신호반응의 종결 • Protein tyrosine phosphatase에 의한 탈인산화 반응 • Receptor의 endocytosis로 lysosome 에서 분해

  10. Epinephrine Insulin ㅑㅜ Glucagon TNFα IR IL-1 Fasting TNFR IL-1R Shc AMPK (AMP) SIRT1 (NAD) TRAF2 IRS-1 IRS-2 TRADD TRAF6 G protein IRAK Cholesterol synthesis MAPKs PI3K NIK HMG-CoA reductase SREBP2 ATP cAMP Cell proliferation Akt IKK Squalene synthase Cyclin D/E PKA NF-κB GSK3 SREBP1 mTOR Glut4 translocation Cell cycle CREB GS Inflammation ChREBP S6K 4E-BP PGC-1α FA synthesis FAS, ACC Glucose uptake S6protein Glycogensynthesis Protein synthesis FOXO HNF-4 Glycolysis FA synthesis Gluconeogenesis PEPCK G6Pase Biosignaling in inflammation and metabolism

  11. Extensive Single DNA Bulky DNA lesion , DNA Excision Repair Single strand breaks IR Radiation DNA Double strand braking Ku Activity ▲ Translocation ATM ATR Wip1 DNA-PK P P P p53 Chk2 Chk1 P P DNA 절단 말단 결합 BRCA1 Wee1 Translocation mdm2 p53 cdc25 Recombinational Repair p21 Cdc2 (CDK1) Cyclin B G2-Phase M-Phase p21 CDK2 CDK2 Cyclin E Cyclin A G1-Phase S-Phase P RB E2F G1-S phase Cell cycle progress RB E2F DNA damage signaling and cell cycle

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