Hsp90 interacts with Cdc37, is phosphorylated by PKA/PKC, and regulates Src phosphorylation in human sperm capacitation
Hsp90 interacts with Cdc37, is phosphorylated by PKA/PKC, and regulates Src phosphorylation in human sperm capacitation
复制标题
Hsp90 与 Cdc37 相互作用，被 PKA/PKC 磷酸化，并调节人类精子获能过程中的 Src 磷酸化
DOI：
10.1111/andr.12862
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发表时间：
2020-07-30
期刊：
影响因子：
4.5
通讯作者：
Ni, Ya
中科院分区：
文献类型：
--
作者：
Li, Kun;Sun, Peibei;Ni, Ya
研究背景热休克蛋白90（Hsp 90）信号通路参与精子获能过程中蛋白质的磷酸化。然而，基本的机制在很大程度上是未知的。目的探讨人精子中热休克蛋白90（Hsp 90）与其辅伴侣蛋白Cdc 37（Cdc 37）的相互作用。材料与方法我们检测了H-89对人乳腺癌细胞的作用，（蛋白激酶A [PKA]抑制剂）和Go 6983（蛋白激酶C [PKC]抑制剂）对Hsp 90中丝氨酸、苏氨酸和酪氨酸残基磷酸化的影响; 17-烯丙基氨基-17-去甲氧基格尔德霉素的作用（17-AAG，Hsp 90抑制剂）对Y 416-Src磷酸化的影响;以及17-AAG和格尔德霉素对人精子获能期间苏氨酸磷酸化的影响。结果Hsp 90与Cdc 37共定位并相互作用。在人精子获能过程中，Hsp 90在丝氨酸、苏氨酸和酪氨酸残基的磷酸化被H-89和Go 6983抑制。此外，酪氨酸激酶Src的活性位点Y 416残基的磷酸化被17-AAG抑制，一些蛋白质的苏氨酸磷酸化水平被17-AAG和格尔德霉素降低。讨论和结论总之，我们的数据表明，热休克蛋白90与Cdc 37的相互作用调节总蛋白苏氨酸磷酸化和Src磷酸化通过其丝氨酸，苏氨酸和酪氨酸磷酸化，这是由PKA和PKC控制在人类精子获能。本研究的结果有助于了解热休克蛋白90调节精子功能的机制。
Background Heat shock protein 90 (Hsp90) signaling pathways participate in protein phosphorylation during sperm capacitation. However, the underlying mechanism is largely unknown. Objective The aim of this study was to explore the interaction between Hsp90 and its co-chaperone protein, cell division cycle protein Cdc37 (Cdc37), in human spermatozoa. Materials and methods We examined the effects of H-89 (a protein kinase A [PKA] inhibitor) and Go6983 (a protein kinase C [PKC] inhibitor) on the phosphorylation of serine, threonine, and tyrosine residues in Hsp90; the effect of 17-allylamino-17-demethoxygeldanamycin (17-AAG, Hsp90 inhibitor) on Y416-Src phosphorylation; and the effects of 17-AAG and geldanamycin on threonine phosphorylation during human sperm capacitation. Results Hsp90 co-localized and interacted with Cdc37. During human sperm capacitation, Hsp90 phosphorylation at serine, threonine, and tyrosine residues was inhibited by H-89 and Go6983. In addition, phosphorylation of residue Y416 in the tyrosine kinase Src (its active site) was inhibited by 17-AAG, and the threonine phosphorylation levels of some proteins were decreased by 17-AAG and geldanamycin. Discussion and conclusion Taken together, our data showed that the interaction of Hsp90 with Cdc37 regulates total protein threonine phosphorylation and Src phosphorylation via its serine, threonine, and tyrosine phosphorylation, which are controlled by PKA and PKC during human sperm capacitation. The results of this study help understand the mechanism underlying Hsp90 regulation of sperm function.