Role of PTEN/PI3K pathway in endothelial cells.

Abstract:

:PTEN (phosphatase and tensin homologue deleted on chromosome 10) is an important tumour-suppressor gene that encodes a 3-phosphatase. The major substrate of PTEN is PIP(3) (phosphatidylinositol 3,4,5-trisphosphate) generated by the action of PI3Ks (phosphoinositide 3-kinases). Hereditary mutation of PTEN causes tumour-susceptibility diseases such as Cowden disease. We used the Cre-loxP system to generate an endothelial cell-specific mutation of PTEN in mice. Heterozygous mutation of PTEN in endothelial cells enhances postnatal neovascularization, including tumour angiogenesis necessary for tumour growth. This observation suggests that Cowden disease patients are not only at risk for additional tumorigenic mutations due to complete loss of PTEN function, but may also experience accelerated growth of incipient tumours due to enhanced angiogenesis. Homozygous mutation of Pten in murine endothelial cells impairs cardiovascular morphogenesis and is embryonic lethal due to endothelial cell hyperproliferation and impaired vascular remodelling. Additional homozygous mutation of p85alpha, the regulatory subunit of class IA PI3Ks, or p110gamma, the catalytic subunit of the sole class IB PI3K, led to a partial rescue of all phenotypes in our PTEN-deficient mice. Thus inhibition of the PI3K pathway, including the targeting of PI3Kgamma, may be an attractive therapeutic strategy for the treatment of various malignancies.

journal_name

Biochem Soc Trans

authors

Suzuki A,Hamada K,Sasaki T,Mak TW,Nakano T

doi

10.1042/BST0350172

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

172-6

issue

Pt 2

eissn

0300-5127

issn

1470-8752

pii

BST0350172

journal_volume

35

pub_type

杂志文章
  • Cytokinesis: the final stop for the chromosomal passengers.

    abstract::The CPC (chromosomal passenger complex) performs essential roles in the regulation and co-ordination of chromosomal and cytoskeletal events during mitosis and meiosis. The first functional analyses showed evidence of a role of the CPC in the regulation of cytokinesis. In this review, I summarize what we have learned s...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0360367

    authors: Carmena M

    更新日期:2008-06-01 00:00:00

  • Molecular aspects of beta-ketoacyl synthase (KAS) catalysis.

    abstract::Crystal structure data for Escherichia coli beta-ketoacyl synthase (KAS) I with C(10) and C(12) fatty acid substrates bound in conjunction with results from mutagenizing residues in the active site leads to a model for catalysis. Differences from and similarities to the other Claisen enzymes carrying out decarboxylati...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/0300-5127:0280601

    authors: von Wettstein-Knowles P,Olsen J,Arnvig Mcguire K,Larsen S

    更新日期:2000-12-01 00:00:00

  • Dissimilatory sulfur cycling in oxygen minimum zones: an emerging metagenomics perspective.

    abstract::Biological diversity in marine OMZs (oxygen minimum zones) is dominated by a complex community of bacteria and archaea whose anaerobic metabolisms mediate key steps in global nitrogen and carbon cycles. Molecular and physiological studies now confirm that OMZs also support diverse micro-organisms capable of utilizing ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20110708

    authors: Stewart FJ

    更新日期:2011-12-01 00:00:00

  • A new detector for fully automatic peptide synthesis.

    abstract::A new method of monitoring the rate of reactions in solid-phase peptide synthesis is described. A conductivity detector in the reaction cell (patent applied for) enables the deprotection, washing and subsequent coupling stages to be examined in detail. The half-lives of the reactions can be calculated and hence the op...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/bst0181308a

    authors: Fox JE

    更新日期:1990-12-01 00:00:00

  • The Escherichia coli cytochrome c maturation (Ccm) apparatus can mature cytochromes with an extra cysteine within or adjacent to the CXXCH motif.

    abstract::c-Type cytochromes are characterized by covalent attachment of haem to protein through thioether bonds between the vinyl groups of the haem and the thiols of a Cys-Xaa-Xaa-Cys-His motif. Proteins of this type play crucial roles in the biochemistry of the nitrogen cycle. Many Gram-negative bacteria use the Ccm (cytochr...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0340091

    authors: Allen JW,Ferguson SJ

    更新日期:2006-02-01 00:00:00

  • Responses of plants to iron, zinc and copper deficiencies.

    abstract::Iron, copper and zinc are essential metals for cell metabolism. Plants have evolved different schemes to efficiently mobilize low-solubility nutrients such as metals from their environment and to transport them between organs. In this review we highlight the divergences and convergences of the iron, copper and zinc up...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/bst0300766

    authors: Wintz H,Fox T,Vulpe C

    更新日期:2002-08-01 00:00:00

  • Functional mapping of Toll/interleukin-1 signalling networks by expression cloning.

    abstract::Multiple cellular proteins have been identified as participating in Toll/interleukin-1 receptor-mediated inflammatory gene expression. The continuing isolation of novel components, based on sequence similarities, protein-protein interactions and protein purification, suggests that many elements of this signalling netw...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20051405

    authors: Kiss-Toth E,Wyllie DH,Holland K,Marsden L,Jozsa V,Oxley KM,Polgar T,Qwarnstrom EE,Dower SK

    更新日期:2005-12-01 00:00:00

  • Metallothioneins and copper metabolism are candidate therapeutic targets in Huntington's disease.

    abstract::HD (Huntington's disease) is caused by a polyQ (polyglutamine) expansion in the huntingtin protein, which leads to protein misfolding and aggregation of this protein. Abnormal copper accumulation in the HD brain was first reported more than 15 years ago. Recent findings show that copper-regulatory genes are induced du...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0380552

    authors: Hands SL,Mason R,Sajjad MU,Giorgini F,Wyttenbach A

    更新日期:2010-04-01 00:00:00

  • Cytochrome P450 (CYP) mutants and substrate-specificity alterations: segment-directed mutagenesis applied to human CYP1A1.

    abstract::Cytochrome P450 (CYP) enzymes represent a large superfamily that displays extraordinarily diverse substrate specificities. After a concise review about CYPs of the CYP1A subfamily, which plays a crucial role in procarcinogen activation, this paper presents segment-directed mutagenesis. This approach generates a librar...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/0300-5127:0290128

    authors: Urban P,Jobert AS,Lainé R,Pompon D

    更新日期:2001-05-01 00:00:00

  • New aspects in cardiac L-type Ca2+ channel regulation.

    abstract::Cardiac excitation-contraction coupling is initiated with the influx of Ca2+ ions across the plasma membrane through voltage-gated L-type calcium channels. This process is tightly regulated by modulation of the channel open probability and channel localization. Protein kinase A (PKA) is found in close association with...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20190229

    authors: Pallien T,Klussmann E

    更新日期:2020-02-28 00:00:00

  • CYP121, CYP51 and associated redox systems in Mycobacterium tuberculosis: towards deconvoluting enzymology of P450 systems in a human pathogen.

    abstract::An extraordinary array of P450 (cytochrome P450) enzymes are encoded on the genome of the human pathogen Mycobacterium tuberculosis (Mtb) and in related mycobacteria and actinobacteria. These include the first characterized sterol 14alpha-demethylase P450 (CYP51), a known target for azole and triazole drugs in yeasts ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0341178

    authors: McLean KJ,Dunford AJ,Sabri M,Neeli R,Girvan HM,Balding PR,Leys D,Seward HE,Marshall KR,Munro AW

    更新日期:2006-12-01 00:00:00

  • Pushing with actin: from cells to pathogens.

    abstract::Actin polymerization is harnessed by cells to generate lamellipodia for movement and by a subclass of pathogens to facilitate invasion of their infected hosts. Using electron tomography (ET), we have shown that lamellipodia are formed via the generation of subsets of actin filaments joined by branch junctions. Image a...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20140184

    authors: Small JV

    更新日期:2015-02-01 00:00:00

  • Exploiting new genome data and Internet resources for the phylogenetic analysis of proteases, substrates and inhibitors.

    abstract::Multiple alignments and phylogenetic tree constructions are established techniques for examining the evolutionary history of protease sequences in organisms such as humans, mice, fruitflies, nematode worms and yeast. They also facilitate the mapping of those conserved positions that are important for structure and cat...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0350599

    authors: Southan C

    更新日期:2007-06-01 00:00:00

  • Applications of bacterial hydrogenases in waste decontamination, manufacture of novel bionanocatalysts and in sustainable energy.

    abstract::Bacterial hydrogenases have been harnessed to the removal of heavy metals from solution by reduction to less soluble metal species. For Pd(II), its bioreduction results in the deposition of cell-bound Pd(0)-nanoparticles that are ferromagnetic and have a high catalytic activity. Hydrogenases can also be used synthetic...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0330076

    authors: Macaskie LE,Baxter-Plant VS,Creamer NJ,Humphries AC,Mikheenko IP,Mikheenko PM,Penfold DW,Yong P

    更新日期:2005-02-01 00:00:00

  • Solid-state NMR spectroscopy as a tool for drug design: from membrane-embedded targets to amyloid fibrils.

    abstract::Structure-based design has gained credibility as a valuable component of the modern drug discovery process. The technique of SSNMR (solid-state NMR) promises to be a useful counterpart to the conventional experimental techniques of X-ray crystallography and solution-state NMR for providing structural features of drug ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0350985

    authors: Middleton DA

    更新日期:2007-11-01 00:00:00

  • A-kinase-anchoring proteins and cytoskeletal signalling events.

    abstract::Targeting of protein kinases and phosphatases to the cytoskeleton enhances the regulation of many signalling events. Cytoskeletal signalling complexes facilitate this process by optimizing the relay of messages from membrane receptors to specific sites on the actin cytoskeleton. These signals influence fundamental cel...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0310087

    authors: Scott JD

    更新日期:2003-02-01 00:00:00

  • Formate and its role in hydrogen production in Escherichia coli.

    abstract::The production of dihydrogen by Escherichia coli and other members of the Enterobacteriaceae is one of the classic features of mixed-acid fermentation. Synthesis of the multicomponent, membrane-associated FHL (formate hydrogenlyase) enzyme complex, which disproportionates formate into CO(2) and H(2), has an absolute r...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0330042

    authors: Sawers RG

    更新日期:2005-02-01 00:00:00

  • The role of LRRK2 in cytoskeletal dynamics.

    abstract::Leucine-rich repeat kinase 2 (LRRK2), a complex kinase/GTPase mutated in Parkinson's disease, has been shown to physically and functionally interact with cytoskeletal-related components in different brain cells. Neurons greatly rely on a functional cytoskeleton for many homeostatic processes such as local and long-dis...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20180469

    authors: Civiero L,Cogo S,Biosa A,Greggio E

    更新日期:2018-12-17 00:00:00

  • The emerging molecular structure of the nitrogen cycle: an introduction to the proceedings of the 10th annual N-cycle meeting.

    abstract::Over the last 10 years, during the lifetime of the nitrogen cycle meetings, structural biology, coupled with spectroscopy, has had a major impact of our understanding enzymology of the nitrogen cycle. The three-dimensional structures for many of the key enzymes have now been resolved and have provided a wealth of info...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0330113

    authors: Butler CS,Richardson DJ

    更新日期:2005-02-01 00:00:00

  • Btk-dependent regulation of phosphoinositide synthesis.

    abstract::Activation of the BCR (B cell antigen receptor) stimulates the production of both PtdIns(3,4,5) P3 and Ins(1,4,5) P3. PtdIns(3,4,5) P3 and Ins(1,4,5) P3 are generated from a common substrate, PtdIns(4,5) P2. In some systems, continuous PtdIns(4,5) P2 synthesis is necessary for maximal Ins(1,4,5) P3 production, but whe...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0320326

    authors: Carpenter CL

    更新日期:2004-04-01 00:00:00

  • Heparan sulphate N-sulphotransferase activity: reaction mechanism and substrate recognition.

    abstract::Human heparan sulphate N-deacetylase/N-sulphotransferase 1 sulphates the NH(3) (+) group of the glucosamine moiety of the heparan chain in heparan sulphate/heparin biosynthesis. An open cleft that runs perpendicular to the sulphate donor 3'-phosphoadenosine 5'-phosphosulphate may constitute the acceptor substrate-bind...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0310331

    authors: Kakuta Y,Li L,Pedersen LC,Pedersen LG,Negishi M

    更新日期:2003-04-01 00:00:00

  • Dissecting DISC1 function through protein-protein interactions.

    abstract::Disrupted in schizophrenia 1 (DISC1) is emerging in the eyes of many as the most promising candidate of all the schizophrenia risk genes. This viewpoint is derived from the combination of genetic, clinical, imaging and rapidly advancing cell biology data around this gene. All of these areas have been reviewed extensiv...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0351283

    authors: Brandon NJ

    更新日期:2007-11-01 00:00:00

  • An unexpected tail of VEGF and PlGF in pre-eclampsia.

    abstract::PET (pre-eclamptic toxaemia), characterized by pregnancy-related hypertension and proteinuria, due to widespread endothelial dysfunction, is a primary cause of maternal morbidity. Altered circulating factors, particularly the VEGF (vascular endothelial growth factor) family of proteins and their receptors, are thought...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20110671

    authors: Bates DO

    更新日期:2011-12-01 00:00:00

  • Role of class II phosphoinositide 3-kinase in cell signalling.

    abstract::Although it is now well established that PI3K (phosphoinositide 3-kinase) is a key enzyme in several intracellular processes, there are still relatively few reports that precisely identify the specific isoforms of PI3K actually involved in such events. The lack of specific inhibitors has made it particularly difficult...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0350211

    authors: Falasca M,Maffucci T

    更新日期:2007-04-01 00:00:00

  • Comparative study of the molecular variation between 'central' and 'peripheral' MUPs and significance for behavioural signalling.

    abstract::MUPs (major urinary proteins) play an important role in chemical signalling in rodents and possibly other animals. In the house mouse (Mus musculus domesticus) MUPs in urine and other bodily fluids trigger a range of behavioural responses that are only partially understood. There are at least 21 Mup genes in the C57BL...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20140082

    authors: Phelan MM,McLean L,Hurst JL,Beynon RJ,Lian LY

    更新日期:2014-08-01 00:00:00

  • EPR experiments to elucidate the structure of the ready and unready states of the [NiFe] hydrogenase of Desulfovibrio vulgaris Miyazaki F.

    abstract::Isolation and purification of the [NiFe] hydrogenase of Desulfovibrio vulgaris Miyazaki F under aerobic conditions leads to a mixture of two states, Ni-A (unready) and Ni-B (ready). The two states are distinguished by different activation times and different EPR spectra. HYSCORE and ENDOR data and DFT calculations sho...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0330007

    authors: van Gastel M,Fichtner C,Neese F,Lubitz W

    更新日期:2005-02-01 00:00:00

  • A novel function of lipid droplets in regulating longevity.

    abstract::Growing evidence supports the view that LDs (lipid droplets) are dynamic organelles that can serve both as an intracellular signalling compartment and as an organizing platform orchestrating many vital processes in eukaryotic cells. It has become clear that the LDs-confined deposition and lipolytic degradation of neut...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0371050

    authors: Goldberg AA,Bourque SD,Kyryakov P,Boukh-Viner T,Gregg C,Beach A,Burstein MT,Machkalyan G,Richard V,Rampersad S,Titorenko VI

    更新日期:2009-10-01 00:00:00

  • TRP channels activated by extracellular hypo-osmoticity in epithelia.

    abstract::TRP (transient receptor potential) channels comprise a superfamily of non-selective cation channels with at least seven subfamilies. The variety of subfamilies corresponds to the differences in the activation mechanisms and functions. TRPM3 (TRP melastatin 3) and TRPV4 (TRP vanilloid 3) have been characterized as cati...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0350091

    authors: Harteneck C,Reiter B

    更新日期:2007-02-01 00:00:00

  • Insights from Drosophila models of Alzheimer's disease.

    abstract::AD (Alzheimer's disease) is a neurodegenerative disorder characterized by the abnormal hyperphosphorylation and aggregation of the microtubule-associated protein tau and the misfolding and deposition of Abeta peptide. The mechanisms by which tau and Abeta become abnormal is not clearly understood, neither is it known ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0380988

    authors: Cowan CM,Shepherd D,Mudher A

    更新日期:2010-08-01 00:00:00

  • Genomic DNA amplification by the multiple displacement amplification (MDA) method.

    abstract::Large amounts of DNA are frequently required for use in detection assays and genomic analysis. The limited availability of DNA can be a critical obstacle to meeting research and clinical needs. DNA amplification methods are often required to generate sufficient material from small specimens or environmental samples wi...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0370450

    authors: Lasken RS

    更新日期:2009-04-01 00:00:00