Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.26 (GSK)
 6,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

G-protein coupled receptor kinases (GRKs) constitute a serine/threonine kinase family playing a major role in agonist-induced phosphorylation and desensitization of G-protein coupled receptors. Recently, GRK2 and GRK5 have been demonstrated to phosphorylate alpha-synuclein (Ser129) and other synuclein isoforms. We studied colocalization of GRK2, GRK5, alpha-synuclein, and tau in neurodegenerative disorders characterized by fibrillary tau inclusions and/or alpha-synuclein-enriched Lewy bodies. We found that Lewy bodies were negative for both GRK2 and GRK5 in Lewy body disease (LBD) and LBD mixed with Alzheimer disease (AD + LBD). Instead, GRK2 but not GRK5 colocalized with 40% to 50% of neurofibrillary tangles in AD + LBD and AD brains. In disorders with less prominent alpha-synucleinopathy, neuronal and glial fibrillary tau deposits known to contain distinct subsets of tau isoforms were also positive for GRK2. These deposits included tufted astrocytes and coiled bodies in progressive supranuclear palsy, astrocytic plaques in corticobasal degeneration, and Pick bodies in Pick disease. In addition, paired helical filaments isolated from AD and AD + LBD brains were found to immunogold-label for GRK2, suggesting that GRK2 could be a potential tau kinase associated with fibrillary tau. Our studies indicate that GRK2 is a novel component of neuronal and glial fibrillary tau deposits with no preference in tau isoform binding. GRK2 may play a role in hyperphosphorylation of tau in tauopathies.
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PMID:Identification of G-protein coupled receptor kinase 2 in paired helical filaments and neurofibrillary tangles. 1714 90

Animals with the neonatal ventral hippocampal lesion (NVHL) demonstrate altered responsiveness to stress and various drugs reminiscent of that in schizophrenia. Post-pubertal onset of abnormalities suggests the possibility of sex differences in NVHL effects that may model sex differences in schizophrenia. Here we demonstrate that novelty- and MK-801-induced hyperactivity is evident in both male and female NVHL rats, whereas only NVHL males were hyperactive in response to apomorphine. Next, we examined the sex- and NVHL-dependent differences in the activity of the ERK and Akt pathways. The basal activity of both pathways was higher in females than in males. NVHL reduces the level of phosphorylation of ERK1/2, Akt, and GSK-3 in both sexes, although males show more consistent down-regulation. Females had higher levels of G-protein-coupled kinases [G-protein-coupled receptor kinase (GRK)] 3 and 5, whereas the concentrations of other GRKs and arrestins were the same. In the nucleus accumbens, the concentration of GRK5 in females was elevated by NVHL to the male level. The data demonstrate profound sex differences in the expression and activity of signalling molecules that may underlie differential susceptibility to schizophrenia.
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PMID:Sex differences in the activity of signalling pathways and expression of G-protein-coupled receptor kinases in the neonatal ventral hippocampal lesion model of schizophrenia. 2015 34