Serine phosphatases

Protein phosphatases that are specific for phosphoserine/ phosphothreonine have a distinct reaction mechanism from tyrosine phosphatases. Protein serine phosphatases are transition metal-dependent, and the reaction mechanism does not involve a phosphoenzyme intermediate as in the case of PTPs. Crystal structures of multiple protein serine phosphatases have revealed how the enzymes catalyze hydrolysis of phosphoserine (14). 

Figure 3 Structure of protein serine phosphatase PP2 C with bound phosphate showing the binuclear metal site (purple spheres) and the nucleophilic water (red sphere). Also shown are residues that ligate the transition metals as well as two key asparagines that coordinate the phosphate group.

Termination of MAP kinase signaling can be accomplished by receptor downregulation, Ras interaction with its GAP, which catalyzes the hydrolysis of GTP on Ras, and by tyrosine and serine phosphatases that disrupt the kinase cascade. Gain of function mutations that... 

Insulin action in the adipocyte results in inhibition of lipolysis. Insulin signals activate AKT/PKB, which phosphorylates and activates PDE-3B [12], This results in cleavage of cAMP by PDE-3B, thus decreasing stimulated lipolysis (Fig. 3). Insulin signaling also activates protein serine phosphatases 1,2A, and 2C which contribute to the dephosphoiylation... 

Redox regulation of signal transduction via protein phosphorylation mechanisms by calcineurin, a threonine/serine phosphatase, is the theme explored by Rusnak and colleagues (Chapter 17). Detailed site-directed mutagenesis and spectroscopic studies reveal the importance of active site amino acid residues and redox state of... 

Th lymphocytes recognize foreign antigens presented by APC cells and, once activated, secrete cytokines that drive cell-mediated immunity (see Figure 56-2). The answer is (E). Cyclosporine inhibits calcineutin, a serine phosphatase that is needed for activation of T cell-specific transcription factors. Gene transcription of IL-2, IL-3, and interferon-y is inhibited. The answer is (D). 

Potts, M., Sun, H., Mockaitis, K., Kennelly, P.J., Reed, D. and Tonks, N.K. (1993) A protein-tyrosine/serine phosphatase encoded by the genome of the cyanobacterium Nostoc commune UTEX 584. Journal of Biological Chemistry 268, 7632-7635. 

Rvl364c 2-COG2208 Serine phosphatase RsbU, regulator of sigma subimit, ... 

Another setback would be to explain the formation of phosphoserine, since a kinase for serine has not been observed. Nemer and Elwyn (21) reported the phosphorylation of radioactive serine by the supernatant fraction of rat liver homogenate. However, this evidently, was a consequence of the exchange reaction between serine and phosphoserine, catalyzed by serine phosphatase (10, 11). This conclusion is supported by the fact that the presence of phosphoserine was required for the reaction and also that ATP was without effect. 

The last part of this account will be devoted to protein kinases and protein phosphatases and some recent results we have obtained for them. Protein kinases and phosphatases are signaling biomolecules that control the level of phosphorylation and dephosphorylation of tyrosine, serine or threonine residues in other proteins, and by this means regulate a variety of fundamental cellular processes including cell growth and proliferation, cell cycle and cytoskeletal integrity. 

Histone phosphorylation is a common posttranslational modification fond in histones, primarily on the N-terminal tails. Phosphorylation sites include serine and threonine residues, tyrosine phosphorylation has not been observed so far. Some phosphorylation events occur locally whereas others occur globally throughout all chromosomes during specific events like mitosis. Histone phosphorylation is catalyzed by kinases. Removal of the phosphoryl groups is catalyzed by phosphatases. 

Phosphorylation is the reversible process of introducing a phosphate group onto a protein. Phosphorylation occurs on the hydroxyamino acids serine and threonine or on tyrosine residues targeted by Ser/Thr kinases and tyrosine kinases respectively. Dephosphorylation is catalyzed by phosphatases. Phosphorylation is a key mechanism for rapid posttranslational modulation of protein function. It is widely exploited in cellular processes to control various aspects of cell signaling, cell proliferation, cell differentiation, cell survival, cell metabolism, cell motility, and gene transcription. 

After their synthesis (translation), most proteins go through a maturation process, called post-translational modification that affects their activity. One common post-translational modification of proteins is phosphorylation. Two functional classes of enzymes mediate this reversible process protein kinases add phosphate groups to hydroxyl groups of serine, threonine and tyrosine in their substrate, while protein phosphatases remove phosphate groups. The phosphate-linking... 

Protein Phosphatases. Figure 2 Families and subtypes of serine/threonine protein phosphatases. 

Cohen PTW (1997) Novel protein serine/threonine phosphatases variety ist he spice of life. Trends Biochem Sci 22 245-251... 

PTEN is a phosphatase, which is a product of a tumor suppressor gene. This phosphatase has an unusual broad specificity and can remove phosphate groups attached to serine, threonine, and tyrosine residues. It is believed that its ability to dephosphorylate phosphati-dylinositol (PI) 3,4,5-triphosphate, the product of PI-3 kinase, is responsible for its tumor suppressor effects. 

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