Substrates were transiently transfected in HEK293, phosphorylated by co-expression with Tyr kinases or PV treatment for 5 min, immunoprecipitated and incubated in phosphatase buffer for 0, 5, 15 and 30 min with either LYP-R620 (LYP-R) or LYP-W620 (LYP-W), the polymorphic variant associated with autoimmune diseases. Here, PTPN22 is linked to autoimmune disease.