SHP-2 tyrosine phosphatase in human diseases.

SHP-2, a ubiquitously expressed Src homology 2 (SH2) domain-containing protein tyrosine phosphatase (PTP), plays a critical role in physiology and disease. SHP-2 has been clearly demonstrated to be an important molecule in various cytoplasmic signal transduction pathways. In addition, emerging evidence indicates that SHP-2 may function in the nucleus and in the mitochondria. However, the signaling mechanisms of SHP-2 are not completely understood. Interestingly, genetic mutations in SHP-2 that either enhance or inactivate its catalytic activity have been identified in human diseases with overlapping phenotypes. In light of this hint given by nature, new cell and animal models now provide the opportunity to uncover how this molecule functions in multiple cellular processes, and more importantly, how its known mutations induce human diseases.