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The Notch pathway is an evolutionary conserved signaling system that regulates cell fate specification, tissue patterning and morphogenesis by modulating cell differentiation, proliferation, apoptosis and survival. In mammals, the core components of the pathway include five canonical DSL (Delta, Serrate, Lag2) ligands (called Dll1,3,4,andJagged1and2) and four single-pass transmembrane receptors (Notch1-4). Since the DSL ligands are membrane-bound, the Notch pathway relies on direct cell-cell interactions for signalgeneration. Ligand binding to the extracellular domain of Notch triggers the proteolytic activation of the
receptor. Juxtamembrane region cleavage of Notch by ADAM metalloproteinase is followed by γ-secretase complex-mediated cleavage and generation of the Notch intracellular domain (NICD). NICD then translocates to the nucleus, where it interacts with the
RBPJ/CSL transcription factor and induces the expression of Notch target genes such as the basic helixloop-helix proteins Hes and Hey.
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真强必胜: 金币+1, ok 2014-03-29 20:15:20
Notch通路是进化过程保留下来的信号系统,通过调节细胞分化,增殖,凋亡和存活掌控细胞特定命运、组织阵列和形态。在哺乳动物中,通路的核心成分包括五种经典的DSL(Delta, Serrate, Lag 2)配体(称为DLL 1,3,4,以及Jagged 1和2)和四个单次跨膜受体(Notch1 - 4)。由于DSL配体是膜结合性质,Notch途径信号产生依赖于直接的细胞 - 细胞相互作用。配体结合的Notch胞外段触发受体的蛋白水解活化。ADAM金属蛋白酶先裂解Notch近膜区,然后γ-分泌酶复合物介导裂解并产生Notch胞内段(NICD)。 NICD然后转移至细胞核,在细胞核与 RBPJ/ CSL转录因子相互作用并诱导如碱性螺旋环 - 螺旋蛋白Hes和Hey的Notch靶基因表达。
2楼2014-03-28 10:07:41
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