SHP-2
SHP-2 (PTPN11) is a ubiquitously expressed non-receptor phosphatase with two SH2 domains preceding its catalytic domain. The N-SH2 domain docks onto phosphotyrosine sites and occludes the active center, so the enzyme switches on only when recruited to activated receptors or scaffolds such as GAB1 and IRS1. Uniquely among protein tyrosine phosphatases, SHP-2 transduces positive signals into the RAS-MAPK pathway. Gain-of-function mutations cause Noonan syndrome and juvenile myelomonocytic leukemia, while loss-of-function variants underlie a form of metachondromatosis, making SHP-2 both a developmental disease gene and an oncology target; allosteric SHP2 inhibitors are now in clinical trials.
