Functional analysis of the tumour suppressor gene PTEN in murine B cells and keratinocytes.

Abstract:

:To investigate the roles of the PTEN (phosphatase and tensin homologue deleted from chromosome 10)/PI3K (phosphoinositide 3-kinase) signalling pathway in vivo, we have generated a series of mutant mice with null or tissue-specific gene-targeted deletions of Pten. Here we present our investigations of Pten function in B cells and keratinocytes in mice. Mice with a B cell-specific mutation of Pten showed increased serum autoantibodies and elevated numbers of B1a cells. Among conventional B (B2) cells in mutant spleens, numbers of marginal zone B cells were significantly increased, while those of follicular B cells were reciprocally decreased. Immunoglobulin class switch recombination was defective and associated with impaired induction of activation-induced cytidine deaminase. Mice with a keratinocyte-specific mutation of Pten exhibited epidermal hyperplasia, hyperkeratosis and accelerated skin morphogenesis. Within 3 weeks of birth, 90% of these animals died of malnutrition, possibly caused by hyperkeratosis of the oesophageal epithelia. Surviving mutant mice developed spontaneous skin tumours within 8.5 months of birth, and chemical treatment accelerated the onset of tumours. Our data show that PTEN is an important regulator in B cells and keratinocytes.

journal_name

Biochem Soc Trans

authors

Suzuki A,Sasaki T,Mak TW,Nakano T

doi

10.1042/bst0320362

keywords:

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

362-5

issue

Pt 2

eissn

0300-5127

issn

1470-8752

journal_volume

32

pub_type

杂志文章,评审
  • Pi sensing and signalling: from prokaryotic to eukaryotic cells.

    abstract::Phosphorus is one of the most important macronutrients and is indispensable for all organisms as a critical structural component as well as participating in intracellular signalling and energy metabolism. Sensing and signalling of phosphate (Pi) has been extensively studied and is well understood in single-cellular or...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20160026

    authors: Qi W,Baldwin SA,Muench SP,Baker A

    更新日期:2016-06-15 00:00:00

  • Heterodimers and family-B GPCRs: RAMPs, CGRP and adrenomedullin.

    abstract::RAMPs (receptor activity-modifying proteins) are single-pass transmembrane proteins that associate with certain family-B GPCRs (G-protein-coupled receptors). Specifically for the CT (calcitonin) receptor-like receptor and the CT receptor, this results in profound changes in ligand binding and receptor pharmacology, al...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0320843

    authors: Conner AC,Simms J,Hay DL,Mahmoud K,Howitt SG,Wheatley M,Poyner DR

    更新日期:2004-11-01 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

  • HAUSP/USP7 as an Epstein-Barr virus target.

    abstract::USP7 (also called HAUSP) is a de-ubiquitinating enzyme recently identified as a key regulator of the p53-mdm2 pathway, which stabilizes both p53 and mdm2. We have discovered that the Epstein-Barr nuclear antigen 1 protein of Epstein-Barr virus binds with high affinity to USP7 and disrupts the USP7-p53 interaction. The...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0320731

    authors: Holowaty MN,Frappier L

    更新日期:2004-11-01 00:00:00

  • Structural insights into chondroitin sulfate binding in pregnancy-associated malaria.

    abstract::Malaria during pregnancy is caused when parasite-infected erythrocytes accumulate within the placenta through interactions between the VAR2CSA protein on the infected erythrocyte surface and placental CSPGs (chondroitin sulfate proteoglycans). This interaction is the major target for therapeutics to treat or prevent p...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0381337

    authors: Khunrae P,Higgins MK

    更新日期:2010-10-01 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

  • The flightless I protein and the gelsolin family in nuclear hormone receptor-mediated signalling.

    abstract::The Drosophila melanogaster flightless I protein and its homologues in higher eukaryotes (FliI) are conserved members of the gelsolin family of actin-binding proteins. Members of the gelsolin family generally contain three or six copies of a 125-amino-acid residue gelsolin-related repeating unit, and may contain addit...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0320940

    authors: Archer SK,Behm CA,Claudianos C,Campbell HD

    更新日期:2004-12-01 00:00:00

  • Modelling the peroxisomal carbon leak during lipid mobilization in Arabidopsis.

    abstract::Mutation of the ACN1 (acetate non-utilizing 1) locus of Arabidopsis results in altered acetate assimilation into gluconeogenic sugars and anapleurotic amino acids and leads to an overall depression in primary metabolite levels by approx. 50% during seedling development. Levels of acetyl-CoA were higher in acn1 compare...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0381230

    authors: Hooks MA,Allen E,Wattis JA

    更新日期:2010-10-01 00:00:00

  • Homomeric protein complexes: evolution and assembly.

    abstract::Homo-oligomeric protein complexes are functionally vital and highly abundant in living cells. In the present article, we review our current understanding of their geometry and evolution, including aspects of the symmetry of these complexes and their interaction interfaces. Also, we briefly discuss the pathway of their...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0380879

    authors: Venkatakrishnan AJ,Levy ED,Teichmann SA

    更新日期:2010-08-01 00:00:00

  • Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein.

    abstract::In the amyloidogenic pathway, the APP (amyloid precursor protein) is proteolytically processed by the beta- and gamma-secretases to release the Abeta (amyloid-beta) peptide that is neurotoxic and aggregates in the brains of patients suffering from Alzheimer's disease. In the non-amyloidogenic pathway, APP is cleaved b...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0330335

    authors: Hooper NM

    更新日期:2005-04-01 00:00:00

  • Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation.

    abstract::Glyoxalase I is part of the glyoxalase system present in the cytosol of cells. The glyoxalase system catalyses the conversion of reactive, acyclic alpha-oxoaldehydes into the corresponding alpha-hydroxyacids. Glyoxalase I catalyses the isomerization of the hemithioacetal, formed spontaneously from alpha-oxoaldehyde an...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0311343

    authors: Thornalley PJ

    更新日期:2003-12-01 00:00:00

  • Insight into stability of CotA laccase from the spore coat of Bacillus subtilis.

    abstract::The axial ligand of the catalytic mononuclear T1 copper site (Met(502)) of the CotA laccase was replaced by a leucine or phenylalanine residue to increase the redox potential of the enzyme. These mutations led to an increase in the redox potential by approx. 100 mV relative to the wild-type enzyme but the catalytic co...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0351579

    authors: Melo EP,Fernandes AT,Durão P,Martins LO

    更新日期:2007-12-01 00:00:00

  • Homologous recombination in the archaea: the means justify the ends.

    abstract::The process of information exchange between two homologous DNA duplexes is known as homologous recombination (HR) or double-strand break repair (DSBR), depending on the context. HR is the fundamental process underlying the genome shuffling that expands genetic diversity (for example during meiosis in eukaryotes). DSBR...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0390015

    authors: White MF

    更新日期:2011-01-01 00:00:00

  • The third extracellular loop of G-protein-coupled receptors: more than just a linker between two important transmembrane helices.

    abstract::GPCRs (G-protein-coupled receptors) are a large family of structurally related proteins, which mediate their effects by coupling with G-proteins. Despite responding to a range of very diverse stimuli, these receptors exhibit a conserved tertiary structure comprising a bundle of seven TM (transmembrane) helices linked ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0321048

    authors: Lawson Z,Wheatley M

    更新日期:2004-12-01 00:00:00

  • ERK5 and its role in tumour development.

    abstract::The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the 'hallmarks o...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20110663

    authors: Lochhead PA,Gilley R,Cook SJ

    更新日期:2012-02-01 00:00:00

  • Comparison of protein repeat classifications based on structure and sequence families.

    abstract::Tandem repeats (TR) in proteins are common in nature and have several unique functions. They come in various forms that are frequently difficult to recognize from a sequence. A previously proposed structural classification has been recently implemented in the RepeatsDB database. This defines five main classes, mainly ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20150079

    authors: Paladin L,Tosatto SC

    更新日期:2015-10-01 00:00:00

  • Characterization of AWAP IV, the C-terminal domain of the avian protein AWAK.

    abstract::AWAP IV constitutes the C-terminal domain of the larger 81 kDa protein AWAK [Avian WAP (whey acidic protein) domain- and Kunitz domain-containing], which is predicted, through conserved domain database searching, to contain at least four WAP domains and one Kunitz domain. RT (reverse transcription)-PCR analyses reveal...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20060267

    authors: Townes CL,Milona P,Hall J

    更新日期:2006-04-01 00:00:00

  • Tuning T helper cell differentiation by ITK.

    abstract::CD4+ effector T cells effectuate T cell immune responses, producing cytokines to orchestrate the nature and type of immune responses. The non-receptor tyrosine kinase IL-2 inducible T cell kinase (ITK), a mediator of T cell Receptor signaling, plays a critical role in tuning the development of these effector cells. In...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20190486

    authors: Elmore JP,McGee MC,Nidetz NF,Anannya O,Huang W,August A

    更新日期:2020-02-28 00:00:00

  • Computational studies of Family A and Family B GPCRs.

    abstract::A full picture of the similarities between Family A and Family B GPCRs (G-protein coupled receptors) has been frustrated by the lack of clear homology between the respective sequences. Here, we review previous computational studies on GPCR dimerization in which the putative dimerization interfaces have been analysed u...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0350749

    authors: Vohra S,Chintapalli SV,Illingworth CJ,Reeves PJ,Mullineaux PM,Clark HS,Dean MK,Upton GJ,Reynolds CA

    更新日期:2007-08-01 00:00:00

  • Tryptophan oxygenation: mechanistic considerations.

    abstract::From a protein structural viewpoint, tryptophan is often considered an inert structural amino acid, playing a role as a hydrophobic anchor in membrane proteins or as part of the hydrophobic core of soluble proteins. However, tryptophan is the only polyaromatic amino acid and, from a chemical viewpoint, possesses uniqu...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20120073

    authors: Naismith JH

    更新日期:2012-06-01 00:00:00

  • Oxidative modification of triacylglycerol-rich lipoproteins.

    abstract::Lipoprotein oxidation is thought to play a pivotal role in the evolution of atherosclerosis. Low-density lipoprotein (LDL) is the main source of oxidized lipid in the arterial wall. Oxidation of LDL alters its properties in a number of ways, making it more atherogenic, but oxidation of other lipoprotein classes may al...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0311062

    authors: Young IS,McFarlane C,McEneny J

    更新日期:2003-10-01 00:00:00

  • Structural dynamics of P-type ATPase ion pumps.

    abstract::P-type ATPases transport ions across biological membranes against concentration gradients and are essential for all cells. They use the energy from ATP hydrolysis to propel large intramolecular movements, which drive vectorial transport of ions. Tight coordination of the motions of the pump is required to couple the t...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20190124

    authors: Dyla M,Basse Hansen S,Nissen P,Kjaergaard M

    更新日期:2019-10-31 00:00:00

  • How do microRNAs regulate gene expression?

    abstract::miRNAs (microRNAs) are short non-coding RNAs that regulate gene expression post-transcriptionally. They generally bind to the 3'-UTR (untranslated region) of their target mRNAs and repress protein production by destabilizing the mRNA and translational silencing. The exact mechanism of miRNA-mediated translational repr...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0361224

    authors: Cannell IG,Kong YW,Bushell M

    更新日期:2008-12-01 00:00:00

  • Managing and sharing experimental data: standards, tools and pitfalls.

    abstract::Experimental processes in the life sciences are becoming increasingly complex. As a result, recording, archiving and sharing descriptions of these processes and of the results of experiments is becoming ever more challenging. However, validation of results, sharing of best practice and integrated analysis all require ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0360033

    authors: Paton NW

    更新日期:2008-02-01 00:00:00

  • Phosphorylation of Zn(II)2Cys6 proteins: a cause or effect of transcriptional activation?

    abstract::Many Zn(II)2Cys6 transcriptional regulators exhibit changes in phosphorylation that are coincident with their roles in transcriptional activation. It is, however, unclear whether these changes occur as a cause of, or as a result of, transcriptional activation. In this paper, we explore the relationship between these t...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0340794

    authors: Leverentz MK,Reece RJ

    更新日期:2006-11-01 00:00:00

  • Immunostimulatory activity of Toll-like receptor 8 agonists towards human leucocytes: basic mechanisms and translational opportunities.

    abstract::TLR8 (Toll-like receptor 8) is activated by ssRNAs (single-stranded RNAs) and synthetic imidazoquinoline compounds that resemble purines and have immunostimulatory activity. TLR8 agonists are particularly effective at inducing Th1-polarizing responses from human monocytes and myeloid dendritic cells, with the magnitud...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0351485

    authors: Philbin VJ,Levy O

    更新日期:2007-12-01 00:00:00

  • Chromosome positioning is largely unaffected in lymphoblastoid cell lines containing emerin or A-type lamin mutations.

    abstract::Gene-poor human chromosomes are reproducibly found at the nuclear periphery in proliferating cells. There are a number of inner nuclear envelope proteins that may have roles in chromosome location and anchorage, e.g. emerin and A-type lamins. In the last decade, a number of diseases associated with tissue degeneration...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20051438

    authors: Meaburn KJ,Levy N,Toniolo D,Bridger JM

    更新日期:2005-12-01 00:00:00

  • Negative feedback in NO/cGMP signalling.

    abstract::Most of the effects of the signalling molecule nitric oxide (NO) are mediated by the stimulation of the NO-sensitive GC (guanylate cyclase) and the subsequent increase in cGMP formation. The enzyme contains a prosthetic haem group, which mediates NO stimulation. In addition to the physiological activator NO, NO-sensit...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20051119

    authors: Koesling D,Mullershausen F,Lange A,Friebe A,Mergia E,Wagner C,Russwurm M

    更新日期:2005-11-01 00:00:00

  • Memapsin 2 (beta-secretase) as a therapeutic target.

    abstract::As beta-secretase, memapsin 2 cleaves amyloid-beta precursor protein, which leads ultimately to the onset of Alzheimer's disease. As such, memapsin 2 is an excellent target of inhibitor drugs for the treatment of this disease. Here we describe the tools for memapsin 2 inhibitor design that have been developed and resu...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0300530

    authors: Hong L,Turner RT 3rd,Koelsch G,Ghosh AK,Tang J

    更新日期:2002-08-01 00:00:00

  • Innate link between NF-kappaB activity and ubiquitin-like modifiers.

    abstract::Among the several signalling pathways regulated by ubiquitin and ubiquitin-like proteins, the one activating NF-kappaB (nuclear factor kappaB) is certainly one of the best characterized. The regulation of the activity of this transcription factor by members of the ubiquitin family occurs at various levels, imposing ov...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0360853

    authors: Lang V,Rodríguez MS

    更新日期:2008-10-01 00:00:00