Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI, USA; School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA.
Cell Rep. 2021 Mar 2;34(9):108796. doi: 10.1016/j.celrep.2021.108796.
Mechanical signals, such as those evoked by maximal-intensity contractions (MICs), can induce an increase in muscle mass. Rapamycin-sensitive signaling events are widely implicated in the regulation of this process; however, recent studies indicate that rapamycin-insensitive signaling events are also involved. Thus, to identify these events, we generate a map of the MIC-regulated and rapamycin-sensitive phosphoproteome. In total, we quantify more than 10,000 unique phosphorylation sites and find that more than 2,000 of these sites are significantly affected by MICs, but remarkably, only 38 of the MIC-regulated events are mediated through a rapamycin-sensitive mechanism. Further interrogation of the rapamycin-insensitive phosphorylation events identifies the S473 residue on Tripartite Motif-Containing 28 (TRIM28) as one of the most robust MIC-regulated phosphorylation sites, and extensive follow-up studies suggest that TRIM28 significantly contributes to the homeostatic regulation of muscle size and function as well as the hypertrophy that occurs in response to increased mechanical loading.
机械信号，如最大强度收缩（MICs）引发的信号，可引起肌肉质量的增加。雷帕霉素敏感的信号事件广泛涉及该过程的调节；然而，最近的研究表明，雷帕霉素不敏感的信号事件也参与其中。因此，为了鉴定这些事件，我们生成了一个 MIC 调节和雷帕霉素敏感的磷酸化蛋白质组图谱。总的来说，我们定量了超过 10000 个独特的磷酸化位点，发现其中超过 2000 个位点受到 MIC 的显著影响，但值得注意的是，只有 38 个 MIC 调节事件是通过雷帕霉素敏感的机制介导的。对雷帕霉素不敏感的磷酸化事件的进一步研究确定了三部分基序结合蛋白 28（TRIM28）上的 S473 残基是最显著的 MIC 调节磷酸化位点之一，广泛的后续研究表明，TRIM28 显著有助于肌肉大小和功能的稳态调节，以及对增加机械负荷的反应性肥大。
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