JNKs (c-Jun N-terminal kinases) belong to the mitogen-activated protein kinase family, and are responsive to stress stimuli, such as cytokines,ultraviolet irradiation, heat shock, and osmotic shock. JNKs play a role in T cell differentiation and the cellular apoptosis pathway. Activation occurs through a dual phosphorylation of threonine (Thr) and tyrosine (Tyr) residues within a Thr-Pro-Tyr motif located in kinase subdomain VIII. Activation is carried out by two MAP kinases, MKK4 and MKK7 and JNK can be inactivated by Ser/Thr and Tyr protein phosphatases. Downstream molecules that are activated by JNK include c-Jun, ATF2, ELK1, SMAD4, p53 and HSF1. JNKs can associate with scaffold proteins JNK interacting proteins as well as their upstream kinases JNKK1 and JNKK2 following their activation. JNK activity regulates several important cellular functions including cell growth, differentiation, survival and apoptosis.
Urolithin B 是 ellagitannins 的肠道微生物代谢产物之一,具有抗炎和抗氧化作用。Urolithin B 通过降低 IκBα 的磷酸化和降解来抑制NF-κB活性。Urolithin B 抑制 JNK、ERK 和 Akt 的磷酸化,增强 AMPK 的磷酸化。Urolithin B 也是骨骼肌质量的调节因子。