Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal transplantation is method of choice for treatment of patients with end-stage renal disease without contraindications for immunosuppressive therapy. Neurological complications occur frequently in renal transplant recipients. They may be the consequence of immunosuppressive treatment, but more often evolve as the consequence of previous disturbances which developed during the state of uraemia and treatment with dialysis. The most pronounced neurotoxic effect has calcineurin inhibitors tacrolimus and cyclosporine. The spectrum of neurological disturbances caused by calcineurin inhibitors range from very mild symptoms as paraesthesiae, tremor, headache or flushing, to severe changes that may cause lethal outcome. Peripheral neuropathies in renal transplant recipients may occur in the form of mononeuropathy or polyneuropathy. Cerebrovascular diseases are consequence of changes on blood vessels caused by uraemia, dialysis and side effects of immunosuppressive drugs. They cause death in 8% of renal transplant recipients. Central nervous system (CNS) infections usually occur during the first posttransplant year. Unclear symptomatology frequently postpones the diagnosis. Diagnostic evaluation should include magnetic resonance imaging for localization of the process, as well as lumbal puncture in cases without contraindications for the procedure, in order to determine the causative agent. Regarding the ominous prognosis of CNS infections in the immunocompromised host, only timely diagnosis may improve survival. The most common causative agents are Cryptococcus neoformans, Listeria monocytogenes and Aspergillus funigatus. Viral infections also occur, and are commonly caused by herpes virideae, varicella-zoster virus and papova virus. CNS infections clinically present as meningitis, progressive dementia or focal neurological defect. The most common primary brain tumors are B-cell lymphomas, but glioblastoma, hemangioblastoma, leiomyosarcoma or glioma may also occur. In cases of neurological posttransplant complications, optimal treatment should be guided by neurologist, nephrologist and infectologist, in some cases also by neurosurgeons.
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PMID:[Neurological complications in renal transplant recipients]. 1857 36

The myosin light chain phosphatase (MLCP) is a cytoskeleton-associated protein phosphatase-1 (PP1) holoenzyme and a RhoA/ROCK effector, regulating cytoskeletal reorganization. ROCK-induced phosphorylation of the MLCP regulatory subunit (MYPT1) at two sites, Thr696 and Thr853, suppresses the activity, although little is known about the difference in the role. Here, we developed a new method for the preparation of the recombinant human MLCP complex and determined the molecular and cellular basis of inhibitory phosphorylation. The recombinant MLCP partially purified from mammalian cell lysates retained characteristics of the native enzyme, such that it was fully active without Mn(2+) and sensitive to PP1 inhibitor compounds. Selective thio-phosphorylation of MYPT1 at Thr696 with ROCK inhibited the MLCP activity 30%, whereas the Thr853 thio-phosphorylation did not alter the phosphatase activity. Interference with the docking of phospho-Thr696 at the active site weakened the inhibition, suggesting selective autoinhibition induced by phospho-Thr696. Both Thr696 and Thr853 sites underwent autodephosphorylation. Compared with that of Thr853, phosphorylation of Thr696 was more stable, and it facilitated Thr853 phosphorylation. Endogenous MYPT1 at Thr696 was spontaneously phosphorylated in quiescent human leiomyosarcoma cells. Serum stimulation of the cells resulted in dissociation of MYPT1 from myosin and PP1C in parallel with an increase in the level of Thr853 phosphorylation. The C-terminal domain of human MYPT1(495-1030) was responsible for the binding to the N-terminal portion of myosin light meromyosin. The spontaneous phosphorylation at Thr696 may adjust the basal activity of cellular MLCP and affect the temporal phosphorylation at Thr853 that is synchronized with myosin targeting.
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PMID:Reconstituted human myosin light chain phosphatase reveals distinct roles of two inhibitory phosphorylation sites of the regulatory subunit, MYPT1. 2471 27