Signal transduction of somatostatin receptors negatively controlling cell proliferation
Signal transduction of somatostatin receptors negatively controlling cell proliferation
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DOI：
10.1016/s0928-4257(00)00206-0
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发表时间：
2000-05-01
影响因子：
--
通讯作者：
Susini, C
中科院分区：
文献类型：
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作者：
Ferjoux, G;Bousquet, C;Susini, C
生长抑素是多种分泌和增殖反应的抑制肽。其作用是由g蛋白偶联受体家族（sst1-5）介导的，该家族可以偶联到多种信号转导途径，如抑制腺苷酸环化酶和鸟苷酸环化酶，调节离子电导通道和蛋白质去磷酸化。这五种受体与天然肽具有高亲和力，但只有sst2、sst5和sst3与短的合成类似物结合。生长抑素负向调节各种正常细胞和肿瘤细胞的生长。这种作用是通过抑制生长促进因子的分泌、血管生成和免疫系统的调节间接介导的。生长抑素也可以直接通过靶细胞上的sst受体起作用。这五种受体在各种正常细胞和肿瘤细胞中表达，每种受体的表达具有受体亚型和细胞类型特异性。根据受体亚型，不同的信号转导途径参与生长抑素的抗增殖作用。Sst1、4和5调节MAP激酶通路，诱导GI细胞周期阻滞。Sst3和sst2分别通过p53依赖性和非依赖性机制促进细胞凋亡。(C) 2000 Elsevier Science Ltd.由Elsevier SAS出版的Editions scientifiques et medicales。
Somatostatin acts as an inhibitory peptide of various secretory and proliferative responses. Its effects are mediated by a family of G-protein-coupled receptors (sst1-5) that can couple to diverse signal transduction pathways such as inhibition of adenylate cyclase and guanylate cyclase, modulation of ionic conductance channels, and protein dephosphorylation. The five receptors bind the natural peptide with high affinity but only sst2, sst5 and sst3 bind the short synthetic analogues. Somatostatin negatively regulates the growth of various normal and tumour cells. This effect is mediated indirectly through inhibition of secretion of growth-promoting factors, angiogenesis and modulation of the immune system. Somatostatin can also act directly through sst receptors present on target cells. The five receptors are expressed in various normal and tumour cells, the expression of each receptor being receptor subtype and cell type specific. According to the receptor subtypes, distinct signal transduction pathways are involved in the antiproliferative action of somatostatin. Sst1, 4 and 5 modulate the MAP kinase pathway and induce GI cell cycle arrest. Sst3 and sst2 promote apoptosis by p53-dependent and -independent mechanisms, respectively. (C) 2000 Elsevier Science Ltd. Published by Editions scientifiques et medicales Elsevier SAS.