Receptor protein phosphatase

Another mechanism of synaptic dysfunction in AD may involve amyloid ft peptide (Aft a 40 to 42 amino acid peptide). A marked increase in Aft levels occurs in brain tissue from AD patients. A ft inhibits glutamatergic neurotransmission and reduces synaptic plasticity (Snyder et al., 2005). Treatment of cortical neuronal cultures with Aft facilitates endocytosis of NMDA receptor. Aft-mediated endo-cytosis of NMDA receptor requires the a-1 nicotinic receptor, protein phosphatase 2B, and the tyrosine phosphatase STEP. Dephosphorylation of the NMDA receptor subunit NR2B at Tyrl472 correlates with receptor endocytosis. The addition of a y-secretase inhibitor not only reduces Aft but also restores surface expression of NMDA receptors, suggesting that A plays an important role in the regulation of NMDA and AMPA receptor trafficking (Snyder et al., 2005 Morishita et al., 2005). 

A secondary metabolite produced by Tolypocladium inflation. This fungus was initially isolated in a soil sample collected in Norway. Cyclosporin A is a cyclic undecapeptide. Inside cells, cyclosporine A binds its immunophillin receptor known as cyclophillin. Like the FK506-FKBP12 complex, cyclosporin A-cyclophillin binds and inhibits the protein phosphatase calcineurin. 

Immunosuppressive Agents Protein Phosphatases Ryanodine Receptor... 

Cyclosporine A (CsA) is a water-insoluble cyclic peptide from a fungus composed of 11 amino acids. CsA binds to its cytosolic receptor cyclophilin. The CsA/cyclophilin complex reduces the activity of the protein phosphatase calcineurin. Inhibition of this enzyme activity interrupts antigen receptor-induced activation and translocation of the transcription factor NEAT to the nucleus which is essential for the induction of cytokine synthesis in T-lymphocytes. 

Dl-iike receptors activate the Gs transduction pathway, stimulating the production of adenylyl cyclase, which increases the formation of cyclic adenosine monophosphate (cAMP) and ultimately increases the activity of cAMP-dependent protein kinase (PKA). PKA activates DARPP-32 (dopamine and cyclic adenosine 3, 5 -monophosphate-regulated phosphoprotein, 32 kDa) via phosphorylation, permitting phospho-DARPP-32 to then inhibit protein phosphatase-1 (PP-1). The downstream effect of decreased PP-1 activity is an increase in the phosphorylation states of assorted downstream effector proteins regulating neurotransmitter... 

Greengard P., Allen P., Nairn A. (1999). Beyond the dopamine receptor the DARPP-32/protein phosphatase-1 cascade. Neuron 23, 435-7. 

Tertoolen, L. G., Blanchetot, C., Jiang, G., Overvoorde, J., Gadella, T. W., Jr., Hunter, T. and den Hertog, J. (2001). Dimerization of receptor protein-tyrosine phosphatase alpha in living cells. BMC Cell Biol. 2, 8. 

Majeti, R. and Weiss, A. (2001). Regulatory mechanisms for receptor protein tyrosine phosphatases. Chem. Rev. 101, 2441-2448. 

Shah, K., Russinova, E., Gadella, T. W., Jr., Willemse, J. and De Vries, S. C. (2002). The Arabidopsis kinase-associated protein phosphatase controls internalization of the somatic embryogenesis receptor kinase 1. Genes Dev. 16,1707-20. 

Brady-Kalnay, S., Rimm, D. and Tonks, N. Receptor protein tyrosine phosphatase PTPm associates with cadherins and catenins in vivo. J. Cell Biol. 130 977-986,1995. 

Flajolet, M., Rakhilin, S., Wang, H. et al. Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3. Proc. Natl Acad. Sci. U.S.A. 16006-16011,2003. 

Receptor protein tyrosine phosphatases consist of an extracellular domain, a transmembrane domain and one or two intracellular catalytic domains 426... 

FIGURE 24-10 Schematic structures of nonreceptor protein tyrosine phosphatases (NRPTPs) and receptor protein tyrosine phosphatases (RPTPs). NRPTPs contain a catalytic domain and various regulatory domains. RPTPs are composed of an extracellular domain, a transmembrane domain and an intracellular domain with one or two catalytic domains. Like receptor protein tyrosine kinases, the structural features of the extracellular domains divide the RPTPs into different families. (With permission from reference [12]). 

Majeti, R., Bilwes, A. M., Noel, J. P. et al. Dimerization-induced inhibition of receptor protein tyrosine phosphatase function through an inhibitory wedge. Science 279 88-91,1998. 

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