Protein tyrosine phosphatase Negative regulation

Other molecules are known to bind the intracellular portion of CD95 and regulate both positively or negatively the cell death signal. EAP-1 is a protein tyrosine phosphatase, which is highly expressed in CD95-resistant... 

Ahmad, E Li, P.-M. Meyerovitch, J. Goldstein, B.J. Osmotic loading of neutrahzing antibodies demonstrates a role of protein-tyrosine phosphatase IB in negative regulation of the insulin action pathway. J. Biol. Chem., 270, 20503-20508 (1995)... 

Although these neurotrophic factors stimulate neurogenesis after brain ischemia, chronic intraventricular administration of peptides or proteins is inappropriate for human therapies because of insufficient penetration into brain tissue. Since various receptor tyrosine kinases, including EGF, FGF-2, BDNF, and VEGF receptors, are negatively regulated by protein tyrosine phosphatases (Ostman and Bohmer, 2001), inhibitors for protein tyrosine phosphatases possibly promote... 

Receptor tyrosine kinases (RTKs) are activated (phosphorylated) by inhibition of a negatively regulating phosphatase upon treatment with UV (A, B, or C), hydrogen peroxide, or iodoacetamide. The phosphatase activity, (i.e., dephosphorylation and inactivation of RTKs) is restored upon the addition of thiol-regenerating agents, if not inhibited irreversibly by iodoacetamide [20]. H2O2 not only inactivates membrane-bound phosphatases but also diminishes cytosolic general protein tyrosine phosphatase activity in mouse fibroblasts [21]. Further, the activation of JNK by sodium arsenite, which is reactive towards thiols (especially vicinal dithiols), is by inactivation of a JNK phosphatase [22]. 

The pathway is negatively regulated by protein tyrosine phosphatases and by feedback inhibition through STAT-mediated expression of suppressors of cytokine signaling (SOCs). Agonists for cytokine receptors are currently used to stimulate red blood cell maturation in anemia (erythropoietin) and to stimulate the immune system (interferons). The cascade nature of the cytokine pathway lends itself to future agents that specifically target components of the pathway. 

Covalent modification is a major mechanism for the rapid and transient regulation of enzyme activity. Numerous enzymes of intermediary metabolism are affected by phosphorylation, either positively or negatively. Covalent phosphorylations can be reversed by a separate subclass of enzymes known as phosphatases. The aberrant phosphorylation of growth factor and hormone receptors, as well as of proteins that regulate cell division, often leads to unregulated cell growth or cancer. The usual sites for phosphate addition to proteins are the serine, threonine and tyrosine R-group hydroxyl residues. 

---