Highly conserved phosphorylation sites.

<p><i>X</i>. <i>laevis</i> phosphosites conserved in human and at least 4 other species are listed with the corresponding human gene name and phosphosite molecular function, if defined in the Phosphosite plus database.</p

Conservation of putative cell-cycle related kinase interactions is predictive of known and/or cell-cycle related kinase-target interactions.

<p>A) The number of predicted kinase target sites and proteins associated with cell-cycle kinases selected for analysis in <i>X</i>. <i>laevis</i>. We tested if the degree of conservation of kinase-interactions was predictive of known interactions; enriched in proteins that are phospho-regulated in the cell cycle; and genes known to cause cell cycle phenotypes when knocked down. B) ROC curves measuring the accuracy for kinase-interaction predictions. C) Enrichment over random prediction for the 3 tested features. D) Predicted kinase interactions conserved in 7 or more species are shown, highlighting known interactions, proteins phospho-regulated during the cell cycle and genes causing cell cycle phonotypes. The edge thickness is proportional to the degree of conseravtion for the predicted kinase-protein interactions. A list of these interactions is provided in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004362#pcbi.1004362.s008" target="_blank">S4 Table</a>.</p

Structural and evolutionary analysis of <i>X</i>. <i>laevis</i> phosphosites.

<p>A) A total of 2636 non-redundant phosphorylation sites were compiled from the sites determined here and those collected from a previous study [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004362#pcbi.1004362.ref029" target="_blank">29</a>]. We determined the conservation of these 2636 phosphorylation sites across the 13 other species and obtained structural models for 518 of these sites. B) The all-atom residue relative surface accessibility was compared for all phospho-acceptor residues, phosphosites not conserved or conserved in at least one other species with available phosphorylation data. C) The fraction of <i>X</i>. <i>laevis</i> sites with a known function in human increases with the degree of conservation. <i>X</i>. <i>laevis</i> sites not conserved in human were excluded from this analysis. D) Example comparative models with highly conserved phosphorylation sites. The phosphorylation site is highlighted in red. For the NDP kinase A, the structure represents the homo-oligomeric complex. One of the subunits is indicated in blue, with the phosphosite position in red and the substrate in the ball-and-stick representation.</p

Identification of a serotonin/glutamate receptor complex implicated in psychosis

The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception.Some antipsychotic drugs were identified by their high affinity for serotonin 5-HT2A receptors (2AR). Drugs that interact with metabotropic glutamate receptors (mGluR) also have potential for the treatment of schizophrenia. The effects of hallucinogenic drugs, such as psilocybin and lysergic acid diethylamide, require the 2AR and resemble some of the core symptoms of schizophrenia. Here we show that the mGluR2 interacts through specific transmembrane helix domains with the 2AR, a member of an unrelated G-protein-coupled receptor family, to form functional complexes in brain cortex. The 2AR-mGluR2 complex triggers unique cellular responses when targeted by hallucinogenic drugs, and activation of mGluR2 abolishes hallucinogen-specific signalling and behavioural responses. In post-mortem human brain from untreated schizophrenic subjects, the 2AR is upregulated and the mGluR2 is downregulated, a pattern that could predispose to psychosis. These regulatory changes indicate that the 2AR-mGluR2 complex may be involved in the altered cortical processes of schizophrenia, and this complex is therefore a promising new target for the treatment of psychosis