Peroxisome proliferator-activated receptor gamma (PPARγ) Serine 273 (PPARγ Ser-273)

Peroxisome proliferator-activated receptor gamma (PPARγ) Ser-273 refers to a specific phosphorylation site on the PPARγ protein that plays a critical role in the development of insulin resistance. In obesity, the kinase CDK5 is activated in adipose tissue, leading to the phosphorylation of PPARγ at Serine 273 (Choi et al., Nature 2010). This modification does not impair the receptor's ability to promote adipogenesis but selectively alters its transcriptional activity, suppressing the expression of insulin-sensitizing adipokines like adiponectin (Choi et al., Nature 2010). Therapeutic targeting of this site aims to inhibit phosphorylation to restore metabolic health. Traditional antidiabetic drugs like thiazolidinediones (TZDs) and newer selective non-agonist ligands, such as SR1664, exert their beneficial effects partly by blocking this phosphorylation (Choi et al., Nature 2011). By focusing on the Ser-273 site, researchers hope to develop treatments for type 2 diabetes that maintain insulin-sensitizing efficacy while minimizing side effects like weight gain and edema (Banks et al., Nature 2015). Consequently, PPARγ Ser-273 serves as a pivotal molecular target for developing safer and more effective metabolic regulators.

Other names

Phospho-PPARγ (Ser273)PPARG Ser273pSer273-PPARγPeroxisome proliferator-activated receptor gamma phosphorylation site Ser273

Inhibition of CDK5-mediated phosphorylation of PPARγ at Serine 273 to restore the expression of insulin-sensitizing genes.