Shp-1 (human), (recombinant)

Shp-1 is one of two human “Src Homology-2 (SH2) containing phosphatases”, enzymes in which two regulatory phosphotyrosine binding domains (N-SH2 & C-SH2) lie N-terminal to the catalytic (PTP) domain. Recruitment of Shp-1 (Src Homology-2 (SH2) containing phosphatase-1) to cell-surface receptors is mediated by SH2-domain binding to “Immuno-receptor Tyrosine-based Inhibitory Motifs” (consensus ITIM: [I/V/L]-x-pY-x-x-[I/V/L]; death receptor variant: A-x-pY-x-x-L). This binding activates Shp-1 phosphatase by displacing an inhibitory interaction between the N-SH2 and PTP domains. By dephosphorylating the downstream elements of various signal transduction pathways, Shp-1 acts as a negative regulator. Shp-1 is highly expressed in hematopoietic cells and to a lesser extent in epithelial cells. It plays a significant role in various stages of hematopoietic development and in limiting neutrophil activation and inflammatory tissue damage through down-regulation of anti-apoptotic, cytokine-derived signals. In most lymphomas and leukemias Shp-1 expression is decreased or absent and Shp-1 may play a role in the pathogenesis of these and other cancers.