Identification of gamma-carboxyglutamic acid residues in mouse ERGP by LC-MS/MS.

Vitamin K (VK) is a micronutrient required for the gamma-carboxylation of secreted proteins. Clinical studies have recently implicated VK in the pathophysiology of diabetes. Our data indicate that rodent beta-cells lacking gamma-carboxylation fail to adapt their insulin secretion in response to glucose in the context of age-related insulin resistance or diet-induced beta-cell stress. In contrast, VK supplementation protects beta-cells from endoplasmic reticulum stress-induced apoptosis. Using anti-Gla immunoprecipitation, we identified ERGP as a putative gamma-carboxylated protein present in pancreatic beta-cells. We used LC-MS/MS to confirm the presence of gamma-carboxyglutamic residues in ERGP.