Characterization of cAMP-dependent proteolysis of GATA-6
Characterization of cAMP-dependent proteolysis of GATA-6
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DOI：
10.1016/j.bbrc.2005.05.042
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发表时间：
2005-07-15
影响因子：
3.1
通讯作者：
Maeda, M
中科院分区：
文献类型：
--
作者：
Ishida, A;Iijima, R;Maeda, M
加塔-6（Delta 50）的环AMP依赖性蛋白水解使用细胞内信号传导途径的抑制剂表征。在这些激酶抑制剂中，只有H-89和K252 a抑制dbcAMP（一种膜渗透性cAMP类似物）诱导的蛋白水解，其它如PD 98059、S13203580、calphostine C、PP 1和KN-93不抑制dbcAMP诱导的蛋白水解。这些结果表明，A-激酶，而不是C-激酶，MEK，P38 MAP-激酶或Src激酶，可以参与所观察到的现象。我们进一步证明，在dbcAMP存在下，泛素异肽酶抑制剂（Delta 12-PGJ 2）抑制加塔-6（Delta 50）的降解，表明cAMP依赖性蛋白水解可以通过泛素-蛋白酶体途径介导，尽管蛋白酶体活性在dbcAMP处理期间没有显著变化。全长加塔-6也响应于诱导的降解。此外，A-和C-激酶的潜在磷酸化位点（Ser-290 -> Ala）的突变和加塔-6的PEST序列的缺失并没有消除降解。所有这些结果表明，细胞因子可能在介导cAMP依赖性过程的激活中起关键作用。(c)2005年爱思唯尔公司All rights reserved.
Cyclic AMP-dependent proteolysis of GATA-6(Delta 50) was characterized using inhibitors for intracellular signaling pathways. Among these kinase inhibitors, only H-89 and K252a inhibited the proteolysis induced by dbcAMP, a membrane permeable cAMP analogue, others such as PD98059, S13203580, calphostine C, PP1, and KN-93 did not do so. These results suggest that A-kinase, but not C-kinase, MEK, P38 MAP-kinases or Src kinase, could participate in the observed phenomenon. We further demonstrated that an inhibitor for ubiquitin isopeptidase (Delta 12-PGJ2) inhibited the degradation of GATA-6(Delta 50) in the presence of dbcAMP, suggesting that the cAMP-dependent proteolysis could be mediated through the ubiquitin-proteasome pathway, although proteasome activity did not change significantly during dbcAMP treatment. The full-length GATA-6 was also responsive to the induced degradation. Furthermore, mutation of a potential phosphorylation site (Ser-290 -> Ala) for A- and C-kinases, and deletion of the PEST sequence of GATA-6 did not abolish the degradation. All these results suggest that cellular factor(s) may play a crucial role in mediating the activation of the cAMP-dependent process. (c) 2005 Elsevier Inc. All rights reserved.