Receptor Interacting Protein Kinase 1 (RIPK1) and RIPK3 are key adaptors that play critical roles in inflammatory and cell death signaling. Work in recent years have shown that their activities are tightly regulated by ubiquitination, phosphorylation and proteolysis. In addition to these post-translational modifications, the expression and activities of these kinases can further be tuned by environmental changes in pH and oxygen content. Proper control of these regulatory processes is crucial for the RIP kinases to execute their functions in immune responses and tissue homeostasis. In this review, we discuss recent advance in our understanding of the molecular mechanisms that regulate the activities of the RIP kinases. We will also discuss how the different regulatory mechanisms contribute to the functions of RIPK1 and RIPK3 in different pathophysiological settings.

受体相互作用蛋白激酶 1 (RIPK1) 和 RIPK3 是在炎症和细胞死亡信号传导中发挥关键作用的关键接头。近年来的研究表明，它们的活性受到泛素化、磷酸化和蛋白水解的严格调控。除了这些翻译后修饰外，这些激酶的表达和活性还可以通过 pH 值和氧含量的环境变化进行进一步调整。正确控制这些调节过程对于 RIP 激酶在免疫反应和组织稳态中执行其功能至关重要。在这篇综述中，我们讨论了我们对调节 RIP 激酶活性的分子机制的理解的最新进展。