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首页> 外文期刊>Cellular Signalling >c-Src is involved in regulating signal transmission from PDGF receptor-GPCR(s) complexes in mammalian cells
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c-Src is involved in regulating signal transmission from PDGF receptor-GPCR(s) complexes in mammalian cells

机译：c-Src参与调节哺乳动物细胞中PDGF受体-GPCR复合物的信号传递

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We have reported that the platelet-derived growth factor receptor-beta (PDGF) forms a novel signaling complex with G protein-coupled receptors (GPCR) (e.g. S1P(1) receptor) that enables more efficient activation of p42/p44 mitogen-activated protein kinase (MAPK) in response to PDGF and sphingosine 1-phosphate (S1P). We now demonstrate that c-Src participates in regulating the endocytosis of PDGFbeta receptor-GPCR complexes in response to PDGF. This leads to association of cytoplasmic p42/p44 MAPK with the receptor complex in endocytic vesicles. c-Src is regulated by G protein betagamma subunits and can interact with beta-arrestin. Indeed, the PDGF-dependent activation of p42/p44 MAPK was reduced by over-expression of the C-terminal domain of GRK2 (sequesters Gbetagamma subunits), the clathrin-binding domain of beta-arrestin and by inhibitors of c-Src and clathrin-mediated endocytosis. Moreover, PDGF and S1P induce the recruitment of c-Src to the PDGFbeta receptor-S1P(1) receptor complex. This leads to a G protein/c-Src-dependent tyrosine phosphorylation of Gab1 and accumulation of dynamin II at the plasma membrane, a step required for endocytosis of the PDGFbeta receptor-GPCR complex. These findings provide important information concerning the molecular organisation of novel receptor tyrosine kinase (RTK)-GPCR signal relays in mammalian cells. (C) 2004 Elsevier Inc. All rights reserved.
机译：我们已经报道了血小板衍生的生长因子受体-β（PDGF）与G蛋白偶联受体（GPCR）（例如S1P（1）受体）形成了一种新型信号复合物，该复合物能够更有效地激活p42 / p44促分裂原活化的蛋白激酶（MAPK）响应PDGF和1磷酸鞘氨醇（S1P）。我们现在证明c-Src参与调节PDGFβ受体-GPCR复合物响应PDGF的内吞作用。这导致胞质p42 / p44 MAPK与内吞小泡中的受体复合物缔合。 c-Src受G蛋白betagamma亚基调控，可与β-arrestin相互作用。确实，PDGF依赖的p42 / p44 MAPK激活通过GRK2的C末端结构域（螯合剂Gbetagamma亚基），β-arrestin的网格蛋白结合结构域以及c-Src和网格蛋白的抑制剂的过表达而降低。介导的内吞作用。此外，PDGF和S1P诱导c-Src募集到PDGFbeta受体-S1P（1）受体复合物。这会导致Gab1的G蛋白/ c-Src依赖性酪氨酸磷酸化和动力蛋白II在质膜上的积累，这是PDGFbeta受体-GPCR复合物内吞的步骤。这些发现提供了有关哺乳动物细胞中新型受体酪氨酸激酶（RTK）-GPCR信号中继的分子组织的重要信息。 （C）2004 Elsevier Inc.保留所有权利。

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