Relevance of c-Src and protein phosphatase 2A to aromatase activity: Evidence of an acute self-regulating oestrogenic signalling complex in rat central nervous system.
Relevance of c-Src and protein phosphatase 2A to aromatase activity: Evidence of an acute self-regulating oestrogenic signalling complex in rat central nervous system.
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DOI：
10.1111/jne.13089
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发表时间：
2022-04
影响因子：
3.2
通讯作者：
Gintzler, Alan R.
中科院分区：
文献类型：
--
作者：
Storman, Emiliya M.;Liu, Nai-Jiang;Gintzler, Alan R.
我们以前报道，芳香酶蛋白水平不平行芳香酶活性。这表明，雌激素信号可能通过芳香酶蛋白的翻译后修饰来调节。已知芳香酶的酪氨酸和丝氨酸磷酸化状态影响其活性。为了研究芳香化酶磷酸化与芳香化酶蛋白及其活性之间观察到的不一致性的可能相关性，我们探索了芳香化酶与酪氨酸激酶c-Src和丝氨酸蛋白磷酸酶2A和5（PP 2A和PP 5）之间的相互作用，以及酪氨酸磷酸化芳香化酶水平与外推芳香化酶活性之间的关系。我们发现：（a）下丘脑芳香化酶的酪氨酸磷酸化程度明显高于脊髓芳香化酶;（B）芳香化酶与c-Src和PP 2A/PP 5发生寡聚化，可能通过酪氨酸磷酸化和丝氨酸去磷酸化激活芳香化酶;（c）c-Src和PP 2A/PP 5与下丘脑芳香化酶的相关性明显高于脊髓芳香化酶;芳香化酶、雌激素受体α、PP 2A和c-Src存在于共同的膜寡聚体中。c-Src和PP 2A在一个寡聚体中的存在，也包含芳香酶和膜雌激素受体α（可能还有其他信号分子），表明CNS中存在一个潜在的自我调节雌激素信号单位。这种复合物自主运作的程度及其调节因素可能具有实质性的生理意义和临床相关性。
We previously reported that aromatase protein levels do not parallel aromatase enzyme activity. This suggests that estrogenic signaling may be modulated via post-translational modification of aromatase protein. The tyrosine and serine phosphorylation state of aromatase are known to influence its activity. To investigate the possible relevance of aromatase phosphorylation to the incongruity observed between aromatase protein and its activity, we explored interactions between aromatase and the tyrosine kinase c-Src and the serine protein phosphatases 2A and 5 (PP2A and PP5), as well as the relationship between levels of tyrosine-phosphorylated aromatase and the extrapolated aromatase activity. We found that (a) hypothalamic aromatase was significantly more heavily tyrosine-phosphorylated than spinal aromatase; (b) aromatase was oligomerized with c-Src and PP2A/PP5, potentially activating aromatase via tyrosine-phosphorylation and serine-dephosphorylation; (c) the associations of c-Src and PP2A/PP5 with hypothalamic aromatase were substantially greater than with spinal aromatase; and (d) aromatase, estrogen receptor α, PP2A, and c-Src were present in a common membrane oligomer. The existence of c-Src and PP2A in an oligomer that also contains aromatase and membrane estrogen receptor α (and presumably other signaling molecules) indicates the presence in the CNS of a potentially self-regulating estrogenic signaling unit. The degree to which such a complex operates autonomously and the regulatory factors thereof are likely to have substantial physiological implications and clinical relevance.
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DOI：
10.1073/pnas.1009923107
发表时间：
2010-11-16
影响因子：
11.1
作者：
Chakrabarti, Sumita;Liu, Nai-Jiang;Gintzler, Alan R.
通讯作者：
Gintzler, Alan R.
影响因子：
3.2
作者：
Remage-Healey L;Oyama RK;Schlinger BA
通讯作者：
Schlinger BA
影响因子：
5.2
作者：
Balthazart J;Charlier TD;Cornil CA;Dickens MJ;Harada N;Konkle AT;Voigt C;Ball GF
通讯作者：
Ball GF
影响因子：
3.4
作者：
Balthazart, J;Baillien, M;Ball, GF
通讯作者：
Ball, GF
影响因子：
3.3
作者：
Prange-Kiel, J;Rune, GM
通讯作者：
Rune, GM