The increased activity of SHP2 reduced the phosphorylation of DOK1, its target protein, at Tyr397, and this was associated with UPP1-uridine production that ultimately facilitated the progression of osteoarthritis.100 Consistent with these findings, SHP2 overexpression activated the WNT/β-catenin signaling pathway to upregulate the downstream proteins involved in matrix degradation. The gene discussed is PTPN11; the disease is osteoarthritis.