Abstract：
Protein kinase A (PKA) is a conserved kinase crucial for fundamental biological processes linked to growth, development, and metabolism. The PKA catalytic subunit is expressed as multiple isoforms in diverse eukaryotes; however, their contribution to ensuring signaling specificity in response to environmental cues remains poorly defined. Catalytic subunit activity is classically moderated via interaction with an inhibitory regulatory subunit. Here, a quantitative mass spectrometry approach is used to examine heat-stress-induced changes in the binding of yeast Tpk1-3 catalytic subunits to the Bcy1 regulatory subunit. We show that Tpk3 is not regulated by Bcy1 binding but, instead, is deactivated upon heat stress via reversible sequestration into cytoplasmic granules. These \"Tpk3 granules\" are enriched for multiple PKA substrates involved in various metabolic processes, with the Hsp42 sequestrase required for their formation. Hence, regulated sequestration of Tpk3 provides a mechanism to control isoform-specific kinase signaling activity during stress conditions.
摘要：
蛋白激酶A（PKA）是一种保守的激酶，对于与生长有关的基本生物过程至关重要。发展,和新陈代谢。PKA催化亚基在不同的真核生物中表达为多个同工型；然而，它们对确保响应环境线索的信号特异性的贡献仍然不明确。催化亚单位活性通常通过与抑制性调节亚单位的相互作用来调节。这里,定量质谱方法用于检查热应激诱导的酵母Tpk1-3催化亚基与Bcy1调节亚基结合的变化。我们表明Tpk3不受Bcy1结合的调节，但是，相反，通过可逆地隔离到胞质颗粒中，在热胁迫下失活。这些“Tpk3颗粒”富含参与各种代谢过程的多种PKA底物，形成所需的Hsp42螯合酶。因此，Tpk3的调节螯合提供了在应激条件下控制同工型特异性激酶信号传导活性的机制。
