However, while animal models of insulin resistance suggest increased ERK signaling as well as an increased phosphorylation of IRS1 on its key activation site S632 (corresponding to S636 in human IRS1; Bouzakri et al., 2003), a significant down-regulation of phosphorylated ERK was observed for both patient-derived fibroblast cell lines. The gene discussed is IRS1; the disease is Insulin resistance.