Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases
Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases
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DOI：
10.1016/s1097-2765(01)00304-5
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发表时间：
2001-08-01
期刊：
影响因子：
16
通讯作者：
Edwards, DP
中科院分区：
文献类型：
--
作者：
Boonyaratanakornkit, V;Scott, MP;Edwards, DP
类固醇激素对细胞信号通路有快速的非基因组效应，但对此负责的受体机制尚不清楚。我们已经在常规孕激素受体(PR)的氨基末端区域中发现了一个特定的多脯氨酸基序，它介导孕激素依赖的PR与包括c-Src酪氨酸激酶在内的各种细胞质信号分子的SH3结构域的直接相互作用。通过这种相互作用，PR是通过SH3结构域置换机制发挥作用的Src激酶的有效激活剂。通过突变，我们还表明，孕激素诱导哺乳动物细胞中Src和下游MAP激酶的快速激活依赖于PR-SH3结构域的相互作用，而不是PR的转录活性。初步证据表明，这个PR信号通路通过调节SH3结构域在影响孕激素诱导的乳腺上皮细胞生长停滞和诱导非洲爪哇卵母细胞成熟方面具有生物学意义。
Steroid hormones have rapid nongenomic effects on cell-signaling pathways, but the receptor mechanisms responsible for this are not understood. We have identified a specific polyproline motif in the amino-terminal domain of conventional progesterone receptor (PR) that mediates direct progestin-dependent interaction of PR with SH3 domains of various cytoplasmic signaling molecules, including c-Src tyrosine kinases. Through this interaction, PR is a potent activator of Src kinases working by an SH3 domain displacement mechanism. By mutagenesis, we also show that rapid progestin-induced activation of Src and downstream MAP kinase in mammalian cells is dependent on PR-SH3 domain interaction, but not on the transcriptional activity of PR. Preliminary evidence for the biological significance of this PR signaling pathway through regulatory SH3 domains was shown with respect to an influence on progestin-induced growth arrest of breast epithelial cells and induction of Xenopus oocyte maturation.