Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been demonstrated that okadaic acid-insensitive protein phosphatases are involved in dephosphorylation of autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in rat cerebellar granule cells (Fukunaga, K., Rich, D. P., and Soderling, T. R. (1989) J. Biol. Chem. 264, 21830-21836). In the present study, recombinant rat protein phosphatase 2C (PrP-2C) expressed in Escherichia coli could dephosphorylate both Thr286/287 and Thr305/306 phosphorylation sites of CaM kinase II, which are responsible for the generation of Ca(2+)-independent activity and the inhibition of the total activity, respectively. The dephosphorylation of Thr286/287 and Thr305/306 was accomplished within 15 min at 0 degrees C and totally dependent on Mg2+. Phosphopeptide mapping of the CNBr-cleaved 32P-labeled CaM kinase II revealed that PrP-2C was relatively specific for dephosphorylation of Thr286/287 and Thr305/306 in the autophosphorylated CaM kinase II. These results suggest that PrP-2C has a role in the regulation of the Ca(2+)-independent activity of CaM kinase II in the neural cells.
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PMID:Dephosphorylation of autophosphorylated Ca2+/calmodulin-dependent protein kinase II by protein phosphatase 2C. 838 Jan 54

Resveratrol shows ability to eliminate prion replication, but the exact mechanism for prion eradication was not clear yet. Our previous studies demonstrate a downregulation of brain-derived nerve growth factor (BDNF) during prion infection, meanwhile recovery of cerebral nerve growth factor (NGF) level by resveratrol treatment has been reported in other neurodegenerative models. To obtain the possible changes of brain NGF and its upstream regulatory cascade during prion infection and after removal of prion propagation, the levels of NGF and its upstream regulatory factors in various prion-infected and prion-eradicated SMB cell lines and mice brains inoculated with various SMB cellular lysates were assessed with various methodologies. The levels of NGF were significantly decreased during prion replication, while recovered after removal of PrPSc by resveratrol in vitro. Morphological assays revealed that the NGF signals mainly colocalized within neurons, but not in the proliferative astrocytes and microglia. The upstream positive regulatory kinases, such as p-CREB, p-CaMKIV, CaMKK2 were decreased in the prion infected cells and mice brains, whereas the negative regulatory one, p-CaMKK2, was increased. The aberrant situations of those kinases in prion infected cell lines or mice brains could be also partially reversed by removal of prion agent. Moreover, we demonstrated that the signals of CaMKK2 and p-CaMKK2 were also distributed predominately in neurons in the brain tissues. The data illustrate a direct linkage of abnormally repressive NGF and its upstream regulatory kinases with prion infection. Resveratrol has not only the ability to inhibit prion replication, but also to improve the expression of NGF via CaMKK2/CaMKIV cascade, which might benefit the microenvironment in brains.
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PMID:The low levels of nerve growth factor and its upstream regulatory kinases in prion infection is reversed by resveratrol. 3189 40