anti-SHP1, mAb (14D5)

SHP1 and SHP2 represent a subfamily of non-transmembrane protein-tyrosine phosphatases (PTPs) that contain two tandem SH2 (src homology 2) domains. SHPs have two N-terminal SH2 domains (N-SH2 and C-SH2), a classic PTP domain and a C-terminal tail harboring two tyrosyl phosphorylation sites which are phosphorylated differentially by receptor and non-receptor protein-tyrosine kinases (PTKs). Whereas SHP2 is expressed ubiquitously, SHP1 is primarily expressed in hematopoietic cells and behaves as a key regulator controlling intracellular phosphotyrosine levels in lymphocytes. SH2 domains (particularly the N-SH2) also regulate PTP activity. Basal SHP activity is low, but addition of a phosphotyrosyl peptide that binds the N-SH2 (Tyr–P peptide ligand) markedly stimulates catalysis. SHP1 is implicated in signaling from receptor tyrosine kinases (RTKs), cytokine receptors, chemokine receptors and integrins. SHP1-deficient bone marrow macrophages are hyper-adherent to β1- and β2-integrin ligands. Decreased SHP1 level causes abnormal T-lymphocyte proliferation and induces various types of leukemias. Introduction of the SHP1 gene back into a leukemia cell line and a prostate cancer cell line demonstrated the tumor suppressor function of SHP1. Plays a key role in hematopoiesis. This PTPase activity may directly link growth factor receptors and other signaling proteins through protein-tyrosine phosphorylation. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation.