Diradourian Claire, Girard Jean, Pégorier Jean-Paul
Département d'Endocrinologie, Institut Cochin, Inserm U567 CNRS UMR8104, Université Paris V, 24, rue du Faubourg Saint Jacques 75014 Paris, France.
Biochimie. 2005 Jan;87(1):33-8. doi: 10.1016/j.biochi.2004.11.010.
In addition to their ligand-mediated activation, nuclear receptor activity is finely tuned by their phosphorylation status. PPARs are phosphorylated by several kinases (PKA, PKC, MAPKs, and AMPK), which affect their activity in a ligand-dependent or -independent manner according to the isoform and cellular context. Molecular consequences are multiple, including changes in ligand affinity, DNA binding, recruitment of transcriptional cofactors, proteasome degradation... Finally, the physiological relevance of PPAR phosphorylation is discussed.
除了其配体介导的激活作用外,核受体活性还通过其磷酸化状态进行精细调节。过氧化物酶体增殖物激活受体(PPARs)可被多种激酶(蛋白激酶A、蛋白激酶C、丝裂原活化蛋白激酶和腺苷酸活化蛋白激酶)磷酸化,这些激酶根据同工型和细胞环境以配体依赖或非依赖的方式影响其活性。分子层面的影响是多方面的,包括配体亲和力的变化、DNA结合、转录辅因子的募集、蛋白酶体降解……最后,还讨论了PPAR磷酸化的生理相关性。