PTPN11

PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11), also known as SHP2 (Src Homology Region 2 domain-containing phosphatase-2), is a non-receptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene in humans. It plays a crucial role in signal transduction pathways that regulate cell growth, differentiation, migration, and apoptosis.

SHP2 is a cytoplasmic protein that functions downstream of receptor tyrosine kinases (RTKs) and cytokine receptors. Upon activation of these receptors, SHP2 is recruited to the receptor complex, where it becomes phosphorylated and activated. Activated SHP2 then dephosphorylates specific phosphotyrosine residues on signaling molecules, thereby modulating their activity and influencing downstream signaling cascades.

PTPN11 is involved in several important signaling pathways, including the RAS-MAPK (mitogen-activated protein kinase) pathway, which is critical for cell growth and proliferation. It also participates in signaling pathways involved in hematopoiesis (blood cell formation), immune cell function, and skeletal development.

Mutations in the PTPN11 gene are associated with a variety of human diseases, including Noonan syndrome, Leopard syndrome, and juvenile myelomonocytic leukemia (JMML). These mutations can result in either gain-of-function or loss-of-function effects, depending on the specific mutation and the cellular context. Gain-of-function mutations, commonly found in Noonan syndrome and JMML, lead to constitutive activation of SHP2, resulting in aberrant signaling and altered cellular behavior. Loss-of-function mutations, observed in some cases of Leopard syndrome, impair SHP2 activity and disrupt normal signaling pathways.

Research on PTPN11 continues to explore its intricate roles in cellular signaling and disease pathogenesis. Targeting PTPN11 is an active area of investigation for the development of novel therapies for cancers and genetic disorders associated with PTPN11 mutations.