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Search Results: 1 - 10 of 2137 matches for " Gerard Manning "
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How the vertebrates were made: selective pruning of a double-duplicated genome
Gerard Manning, Eric Scheeff
BMC Biology , 2010, DOI: 10.1186/1741-7007-8-144
Abstract: See research article: http://www.biomedcentral.com/1741-7007/8/146/abstract webciteA doubling of the genome, or whole genome duplication (WGD), is usually a cataclysmic event for an organism. Yet this polyploidy has been an important, if rare, event in the evolution of many plant groups, and has also occurred in yeasts, ciliates, fish and frogs [1]. It is now generally accepted that we and all other jawed vertebrates are the product of a remarkable two rounds of WGD, known as 2R [2], which duplicated every gene up to four-fold (fish and frog genomes have undergone a third duplication more recently). This opened the door to a tremendous expansion in functionality, and while most WGD duplicates, or ohnologs, were rapidly lost, this phenomenon was the genesis of almost one-third of all human genes. Establishing why these duplicates were retained and how they have evolved since then is an important way to advance the understanding of their current functions.A study by Huminiecki and Heldin in BMC Biology [3] seeks to answer these questions through a global analysis of genes that survived the massive pruning that followed 2R. They identified 2R-derived gene pairs using a combination of sequence similarity (by comparing gene trees with the underlying species trees to identify duplications [4]) and chromosomal location, using syntenic chromosomal regions, in which runs of related gene pairs occur in different loci. They then explore the history of most vertebrate genes through 2R and subsequent gains and losses. They find that retained ohnologs are highly biased towards signaling genes and transcription factors and argue that this large pool of new genes would have enabled the complex regulation required for the development and function of the vertebrate body plan. They integrate these results with expression and pathway data to show that retained ohnologs play important roles in functional categories, such as those required by the nervous system and for locomotion, that a
Amphioxus encodes the largest known family of green fluorescent proteins, which have diversified into distinct functional classes
Erin K Bomati, Gerard Manning, Dimitri D Deheyn
BMC Evolutionary Biology , 2009, DOI: 10.1186/1471-2148-9-77
Abstract: The amphioxus genome encodes 16 closely-related GFP-like proteins, all of which appear to be under purifying selection. We divide them into 6 clades based on protein sequence identity and show that representatives of each clade have significant differences in fluorescence intensity, extinction coefficients, and absorption profiles. Furthermore, GFPs from two clades exhibit antioxidant capacity. We therefore propose that amphioxus GFPs have diversified their functions into fluorescence, redox, and perhaps just light absorption in relation to pigmentation and/or photoprotection.The rapid radiation of amphioxus GFP into clades with distinct functions and spectral properties reveals functional plasticity of the GFP core. The high sequence similarities between different clades provide a model system to map sequence variation to functional changes, to better understand and engineer GFP.The discovery of green fluorescent protein (GFP) in the bioluminescent jellyfish Aequorea victoria [1] sparked the interest of marine ecologists, cell biologists, and spectroscopists alike. The subsequent cloning [2] and characterization [3,4] of GFP revealed that its energy-absorbing core, the chromophore, is self-generated via cyclization of a peptide triplet buried in the interior of a protective β-can protein fold [5,6]. Once oxidized using molecular oxygen, the chromophore shows high stability and absorbance of high-energy light (blue) that is efficiently re-emitted as fluorescence of lower-energy (green) light over a wide range of conditions. The ease of expression of GFP in a variety of hosts has enabled a myriad of fluorescence imaging applications, from quantifying transgene expression to probing enzyme activity and protein-protein interactions [7-10]. Its tremendous utility was recognized by the award of the 2008 Nobel prize in Chemistry.Since the discovery of GFP in Aequorea victoria, researchers have identified GFP-like proteins from other cnidarians with distinctive biochemical
The dictyostelium kinome--analysis of the protein kinases from a simple model organism.
Goldberg Jonathan M,Manning Gerard,Liu Allen,Fey Petra
PLOS Genetics , 2006,
Abstract: Dictyostelium discoideum is a widely studied model organism with both unicellular and multicellular forms in its developmental cycle. The Dictyostelium genome encodes 285 predicted protein kinases, similar to the count of the much more advanced Drosophila. It contains members of most kinase classes shared by fungi and metazoans, as well as many previously thought to be metazoan specific, indicating that they have been secondarily lost from the fungal lineage. This includes the entire tyrosine kinase-like (TKL) group, which is expanded in Dictyostelium and includes several novel receptor kinases. Dictyostelium lacks tyrosine kinase group kinases, and most tyrosine phosphorylation appears to be mediated by TKL kinases. About half of Dictyostelium kinases occur in subfamilies not present in yeast or metazoa, suggesting that protein kinases have played key roles in the adaptation of Dictyostelium to its habitat. This study offers insights into kinase evolution and provides a focus for signaling analysis in this system.
The Raine Syndrome Protein FAM20C Is a Golgi Kinase That Phosphorylates Bio-Mineralization Proteins
Hiroyuki O. Ishikawa, Aiguo Xu, Eri Ogura, Gerard Manning, Kenneth D. Irvine
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042988
Abstract: Raine syndrome is caused by mutations in FAM20C, which had been reported to encode a secreted component of bone and teeth. We found that FAM20C encodes a Golgi-localized protein kinase, distantly related to the Golgi-localized kinase Four-jointed. Drosophila also encode a Golgi-localized protein kinase closely related to FAM20C. We show that FAM20C can phosphorylate secreted phosphoproteins, including both Casein and members of the SIBLING protein family, which modulate biomineralization, and we find that FAM20C phosphorylates a biologically active peptide at amino acids essential for inhibition of biomineralization. We also identify autophosphorylation of FAM20C, and characterize parameters of FAM20C’s kinase activity, including its Km, pH and cation dependence, and substrate specificity. The biochemical properties of FAM20C match those of an enzymatic activity known as Golgi casein kinase. Introduction of point mutations identified in Raine syndrome patients into recombinant FAM20C impairs its normal localization and kinase activity. Our results identify FAM20C as a kinase for secreted phosphoproteins and establish a biochemical basis for Raine syndrome.
Structural and Functional Diversity of the Microbial Kinome
Natarajan Kannan,Susan S. Taylor,Yufeng Zhai,J. Craig Venter,Gerard Manning
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0050017
Abstract: The eukaryotic protein kinase (ePK) domain mediates the majority of signaling and coordination of complex events in eukaryotes. By contrast, most bacterial signaling is thought to occur through structurally unrelated histidine kinases, though some ePK-like kinases (ELKs) and small molecule kinases are known in bacteria. Our analysis of the Global Ocean Sampling (GOS) dataset reveals that ELKs are as prevalent as histidine kinases and may play an equally important role in prokaryotic behavior. By combining GOS and public databases, we show that the ePK is just one subset of a diverse superfamily of enzymes built on a common protein kinase–like (PKL) fold. We explored this huge phylogenetic and functional space to cast light on the ancient evolution of this superfamily, its mechanistic core, and the structural basis for its observed diversity. We cataloged 27,677 ePKs and 18,699 ELKs, and classified them into 20 highly distinct families whose known members suggest regulatory functions. GOS data more than tripled the count of ELK sequences and enabled the discovery of novel families and classification and analysis of all ELKs. Comparison between and within families revealed ten key residues that are highly conserved across families. However, all but one of the ten residues has been eliminated in one family or another, indicating great functional plasticity. We show that loss of a catalytic lysine in two families is compensated by distinct mechanisms both involving other key motifs. This diverse superfamily serves as a model for further structural and functional analysis of enzyme evolution.
Structural and Functional Diversity of the Microbial Kinome
Natarajan Kannan,Susan S Taylor,Yufeng Zhai,J. Craig Venter,Gerard Manning
PLOS Biology , 2007, DOI: 10.1371/journal.pbio.0050017
Abstract: The eukaryotic protein kinase (ePK) domain mediates the majority of signaling and coordination of complex events in eukaryotes. By contrast, most bacterial signaling is thought to occur through structurally unrelated histidine kinases, though some ePK-like kinases (ELKs) and small molecule kinases are known in bacteria. Our analysis of the Global Ocean Sampling (GOS) dataset reveals that ELKs are as prevalent as histidine kinases and may play an equally important role in prokaryotic behavior. By combining GOS and public databases, we show that the ePK is just one subset of a diverse superfamily of enzymes built on a common protein kinase–like (PKL) fold. We explored this huge phylogenetic and functional space to cast light on the ancient evolution of this superfamily, its mechanistic core, and the structural basis for its observed diversity. We cataloged 27,677 ePKs and 18,699 ELKs, and classified them into 20 highly distinct families whose known members suggest regulatory functions. GOS data more than tripled the count of ELK sequences and enabled the discovery of novel families and classification and analysis of all ELKs. Comparison between and within families revealed ten key residues that are highly conserved across families. However, all but one of the ten residues has been eliminated in one family or another, indicating great functional plasticity. We show that loss of a catalytic lysine in two families is compensated by distinct mechanisms both involving other key motifs. This diverse superfamily serves as a model for further structural and functional analysis of enzyme evolution.
Hepatic Solitary Fibrous Tumor Presenting as Severe Hypoglycaemia: A Case-Report  [PDF]
Thomas E. Manning, Anna E. Manning, Patrick J. Manning
Case Reports in Clinical Medicine (CRCM) , 2015, DOI: 10.4236/crcm.2015.42014
Abstract:
We report a case of a patient presenting with profound insulin-independent hypoglycaemia. A large hepatic leasion was identified and surgically resected. Histology confirmed a 17.5 cm hepatic solitary fibrous tumour. The clinical and biochemical presentation is consistent with IGF-II mediated hypoglycaemia.
The minimal kinome of Giardia lamblia illuminates early kinase evolution and unique parasite biology
Gerard Manning, David S Reiner, Tineke Lauwaet, Michael Dacre, Alias Smith, Yufeng Zhai, Staffan Svard, Frances D Gillin
Genome Biology , 2011, DOI: 10.1186/gb-2011-12-7-r66
Abstract: To explore early kinase evolution and regulation of Giardia biology, we cataloged the kinomes of three sequenced strains. Comparison with published kinomes and those of the excavates Trichomonas vaginalis and Leishmania major shows that Giardia's 80 core kinases constitute the smallest known core kinome of any eukaryote that can be grown in pure culture, reflecting both its early origin and secondary gene loss. Kinase losses in DNA repair, mitochondrial function, transcription, splicing, and stress response reflect this reduced genome, while the presence of other kinases helps define the kinome of the last common eukaryotic ancestor. Immunofluorescence analysis shows abundant phospho-staining in trophozoites, with phosphotyrosine abundant in the nuclei and phosphothreonine and phosphoserine in distinct cytoskeletal organelles. The Nek kinase family has been massively expanded, accounting for 198 of the 278 protein kinases in Giardia. Most Neks are catalytically inactive, have very divergent sequences and undergo extensive duplication and loss between strains. Many Neks are highly induced during development. We localized four catalytically active Neks to distinct parts of the cytoskeleton and one inactive Nek to the cytoplasm.The reduced kinome of Giardia sheds new light on early kinase evolution, and its highly divergent sequences add to the definition of individual kinase families as well as offering specific drug targets. Giardia's massive Nek expansion may reflect its distinctive lifestyle, biphasic life cycle and complex cytoskeleton.Protein kinases modulate most cellular pathways, particularly in the co-ordination of complex cellular processes and in response to environmental signals. About 2% of genes in most eukaryotes encode kinases, and these kinases phosphorylate over 30% of the proteome [1]. Kinases regulate the activity, localization and turnover of their substrates. Most kinases have dozens of substrates, and operate in complex, multi-kinase cascades. H
Classifying Groups of Small Order  [PDF]
Gerard Thompson
Advances in Pure Mathematics (APM) , 2016, DOI: 10.4236/apm.2016.62007
Abstract: The classification of groups of order less than 16 is reconsidered. The goal of the paper is partly historical and partly pedagogical and aims to achieve the classification as simply as possible in a way which can be easily incorporated into a first course in abstract algebra and without appealing to the Sylow Theorems. The paper concludes with some exercises for students.
The Dictyostelium Kinome—Analysis of the Protein Kinases from a Simple Model Organism
Jonathan M Goldberg equal contributor,Gerard Manning equal contributor,Allen Liu,Petra Fey,Karen E Pilcher,Yanji Xu,Janet L Smith
PLOS Genetics , 2006, DOI: 10.1371/journal.pgen.0020038
Abstract: Dictyostelium discoideum is a widely studied model organism with both unicellular and multicellular forms in its developmental cycle. The Dictyostelium genome encodes 285 predicted protein kinases, similar to the count of the much more advanced Drosophila. It contains members of most kinase classes shared by fungi and metazoans, as well as many previously thought to be metazoan specific, indicating that they have been secondarily lost from the fungal lineage. This includes the entire tyrosine kinase–like (TKL) group, which is expanded in Dictyostelium and includes several novel receptor kinases. Dictyostelium lacks tyrosine kinase group kinases, and most tyrosine phosphorylation appears to be mediated by TKL kinases. About half of Dictyostelium kinases occur in subfamilies not present in yeast or metazoa, suggesting that protein kinases have played key roles in the adaptation of Dictyostelium to its habitat. This study offers insights into kinase evolution and provides a focus for signaling analysis in this system.
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