Disease relevance of PHLPP

• Reintroduction of PHLPP into a glioblastoma cell line causes a dramatic suppression of tumor growth [1].
• PHLPP levels are markedly reduced in several colon cancer and glioblastoma cell lines that have elevated Akt phosphorylation [1].
• Transderm Scop for prevention of motion sickness [2].
• More than 80% of all the folds in the SCOP structural classification were identified in one of the 20 organisms, with worm and E. coli having the largest number of distinct folds [3].

High impact information on PHLPP

• Moreover, training for novel object memory decreases SCOP in the hippocampus [4].
• To determine if hippocampus-dependent memory is influenced by SCOP in vivo, we generated a transgenic mouse strain for the inducible overexpression of SCOP in the forebrain [4].
• PHLPP and a Second Isoform, PHLPP2, Differentially Attenuate the Amplitude of Akt Signaling by Regulating Distinct Akt Isoforms [5].
• Here, we identify a protein phosphatase, PH domain leucine-rich repeat protein phosphatase (PHLPP), that specifically dephosphorylates the hydrophobic motif of Akt (Ser473 in Akt1), triggering apoptosis and suppressing tumor growth [1].
• PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth [1].

Biological context of PHLPP

• Doing so involves an all-vs.-all comparison of protein domains [taken here from the Structural Classification of Proteins (scop) database] and then fitting a simple distribution function to the observed scores [6].
• Our tree is largely in agreement with results from the structural classification of proteins (SCOP), a multidimensional classification based on homologous sequences, full three-dimensional structure, information about chemistry and evolution, and human judgment [7].
• We find 783 out of the 859 superfamilies in SCOP in these genomes, and the 783 families occur in 1307 pairwise combinations [8].
• Analysis of CATH and SCOP revealed the significant contribution that structural genomics is making to the coverage of superfamilies and folds [9].
• However, 50 cases were identified in which SCOP domains are disrupted in the middle by alternative splicing [10].

Anatomical context of PHLPP

• SCOP, a novel gene product expressed in a circadian manner in rat suprachiasmatic nucleus [11].
• Soils and plant parts belonging to Thymus praecox Opiz., Acinos alpinus (L.) Moench, Plantago holosteum Scop and Festuca punctoria Sm species collected from three directions around Wolfram Mine Work were used for our investigations [12].
• Neurosecretory cells in the brain, ventral ganglia, and retrocerebral endocrine glands aortal complex of a milkweed bug, Lygaeus pandurus Scop. have been described using a variety of techniques in whole mounts and sections [13].
• Behavioral studies in rats have demonstrated that the medial septum/diagonal band of Broca (MSDB), which sends cholinergic and GABAergic projections to the hippocampus, is a critical locus in mediating the amnesic effects of atr/scop [14].

Associations of PHLPP with chemical compounds

• The Sequence Alignment Benchmark (SABmark) provides sets of multiple alignment problems derived from the SCOP classification [15].
• Effect of bioactive compounds from Sainfoin ( Onobrychis viciifolia Scop.) on the in vitro larval migration of Haemonchus contortus: role of tannins and flavonol glycosides [16].
• From these results, we suggest that the attenuating effect of luteolin (10 mg/kg, i.p.) on the deficits of passive avoidance performance induced by SCOP may be related to the increases in the activities of central muscarinic and nicotinic receptors [17].
• The effects of phorate and some of its metabolites incorporated in an artificial diet on liquid uptake by Aphis fabae scop [18].
• Luteolin was not reversed by scopolamine N-methylbromide (M-SCOP) but blocked the impairment of learning acquisition induced by cholinergic neurotoxin (ethylcholine aziridinium, AF64A) and muscarinic (scopolamine hydrobromide, SCOP) and nicotinic (mecamylamine, MECA) receptor antagonists [17].
• Knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha [19].

Analytical, diagnostic and therapeutic context of PHLPP

• We use the Structural Classification of Proteins (SCOP) database to link sequence alignments from the SMART and Pfam databases [20].
• Structure and sequence analysis of several metal-binding proteins reveals unexpected similarities in structural domains classified as different protein folds in SCOP and suggests unification of seven folds that belong to two protein classes [21].
• Micellar electrokinetic chromatography (MEKC) was used for the separation and determination of two iridoid glycosides, aucubin and catalpol, in several Plantago species growing in Croatia: P. altissima L., P. argentea Chaix, P. coronopus L., P. holosteum Scop [22].

References