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首页> 外文期刊>Endocrinology >Characterization of intracellular signaling mediated by human somatostatin receptor 5: role of the DRY motif and the third intracellular loop.
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Characterization of intracellular signaling mediated by human somatostatin receptor 5: role of the DRY motif and the third intracellular loop.

机译：人生长抑素受体5介导的细胞内信号转导的特征：DRY基序和第三个细胞内环的作用。

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Somatostatin (SST) exerts inhibitory effects on hormone secretion and cell proliferation by interacting with five different receptors (SST1-SST5) linked to multiple cellular effectors. The receptor structural domains involved in these effects have been only partially elucidated. The aim of the study was to investigate the molecular determinants mediating the interaction of the human SST5 with intracellular signaling in the pituitary cell line GH3, focusing on the BBXXB domain in the third intracellular loop and the DRY motif in the second intracellular loop. We analyzed the effects of the SST5 agonist BIM23206 on cAMP accumulation, intracellular calcium, GH secretion, cell proliferation, and ERK1/2 phosphorylation in cells expressing either wild-type SST5 or mutant receptors, in particular the naturally occurring mutant R240W in the BBXXB domain and the D136A and R137A mutants in the DRY motif. We found that residues D136 and R137 were critical for SST5 signaling because their substitutions abolished all the intracellular responses. Conversely, third intracellular loop mutations resulted in receptor that inhibited intracellular cAMP levels similar to the wild-type (50 +/- 9 vs. 53 +/- 12% inhibition) but failed to mediate the other responses elicited by wild-type SST5, i.e. reduction of intracellular calcium levels as well as inhibition of ERK1/2. These events resulted in an absent inhibition of GH release and an impaired reduction of cell proliferation (38 +/- 7 vs. 76 +/- 6% inhibition in wild type, P < 0.05). These data indicate that different regions of SST5 are required for the activation of different signaling pathways.
机译：生长抑素（SST）通过与五个与多个细胞效应子相连的不同受体（SST1-SST5）相互作用，对激素分泌和细胞增殖产生抑制作用。与这些作用有关的受体结构域仅被部分阐明。该研究的目的是研究介导人SST5与垂体细胞系GH3中细胞内信号传导相互作用的分子决定簇，重点研究第三细胞内环中的BBXXB结构域和第二细胞内环中的DRY基序。我们分析了SST5激动剂BIM23206对表达野生型SST5或突变受体，特别是BBXXB域中天然存在的突变R240W的细胞中cAMP积累，细胞内钙，GH分泌，细胞增殖和ERK1 / 2磷酸化的影响DRY基序中的D136A和R137A突变体。我们发现，残基D136和R137对于SST5信号传导至关重要，因为它们的取代消除了所有细胞内应答。相反，第三次细胞内环突变导致受体抑制细胞内cAMP的水平类似于野生型（50 +/- 9 vs. 53 +/- 12％抑制），但无法介导野生型SST5引起的其他反应，即降低细胞内钙水平以及抑制ERK1 / 2。这些事件导致GH释放的抑制被抑制和细胞增殖的减少受损（野生型抑制为38 +/- 7对76 +/- 6％，P <0.05）。这些数据表明，激活不同的信号通路需要SST5的不同区域。

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