Wyniki wyszukiwania - Biblioteka Nauki

1

Lipids and signal transduction in the nucleus.

100%

Dygas A. , Barańska J.

Acta Biochimica Polonica

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2001

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tom 48

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nr 2

541-549

EN

During the last few years a growing amount of data has accumulated showing phospholipid participation in nuclear signal transduction. Very recent data strongly support the hypothesis that signal transduction in the nucleus is autonomic. Local production of inositol polyphosphates, beginning with the activation of phospholipase C is required for their specific function in the nucleus. Enzymes which modify polyphosphoinositols may control gene expression. Much less information is available about the role of other lipids in nuclear signal transduction. The aim of this minireview is to stress what is currently known about nuclear lipids with respect to nuclear signal transduction.

2

Signal transmission via G protein-coupled receptors in the light of rhodopsin structure determination.

80%

Ciarkowski J. , Drabik P. , Giełdoń A. , Kaźmierkiewicz R. , Ślusarz R.

Acta Biochimica Polonica

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2001

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tom 48

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nr 4

1203-1207

EN

G protein-coupled receptors (GPCRs) transducing diverse external signals to cells via activation of heterotrimeric GTP-binding (G) proteins, estimated to mediate actions of 60% of drugs, had been resistant to structure determination until summer 2000. The first atomic-resolution experimental structure of a GPCR, that of dark (inactive) rhodopsin, thus provides a trustworthy 3D prototype for antagonist-bound forms of this huge family of proteins. In this work, our former theoretical GPCR models are evaluated against the new experimental template. Subsequently, a working hypothesis regarding the signal transduction mechanism by GPCRs is presented.

3

Hydrolysis of cyclic GMP in rat peritoneal macrophages.

80%

Witwicka H. , Kobiałka M. , Gorczyca W. A.

Acta Biochimica Polonica

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2002

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tom 49

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nr 4

891-897

EN

Intact rat peritoneal macrophages (rPM) treated with 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterases (PDEs), accumulated more cGMP than untreated cells. A PDE activity toward [3H]cGMP was detected in the soluble and particulate fractions of rPM. The hydrolysis of cGMP was Ca2+/calmodulin-independent but increased in the presence of cGMP excess. Similar results were obtained when [3H]cAMP was used as a substrate. The hydrolytic activity towards both nucleotides was inhibited in the presence of IBMX. Therefore, the PDEs of families 2, 5, 10 and 11 are potential candidates for cGMP hydrolysis in the rPM. They may not only regulate the cGMP level in a feedback-controlled way but also link cGMP-dependent pathways with those regulated by cAMP.

4

Lipids and signal transduction in the nucleus

80%

Dygas A. , Baranska J.

Acta Biochimica Polonica

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2001

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tom 48

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nr 2

EN

During the last few years a growing amount of data has accumulated showing phospholipid par tic i pa tion in nu clear sig nal transduction. Very re cent data strongly sup port the hy poth e sis that sig nal transduction in the nu cleus is au to nomic. Lo cal pro duc tion of inositol polyphosphates, be gin ning with the ac ti va tion of phospholipase C is required for their specific function in the nucleus. Enzymes which modify poly- phosphoinositols may control gene expression. Much less information is available about the role of other lipids in nuclear signal transduction. The aim of this minireview is to stress what is cur rently known about nu clear lipids with re spect to nu clear sig nal transduction.

5

The emerging distinct role of TNF-receptor 2 [p80] signalling in chronic inflammatory disorders

80%

Holtmann M. H. , Schuchmann M. , Zeller G. , Galle P. R. , Neurath M. F.

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tom 50

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nr 4

6

Dissecting the functions of protein tyrosine phosphatases using chemical approaches

80%

Zhang Z. Y.

Cellular and Molecular Biology Letters

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2005

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tom 10

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nr Suppl.2

7

Negative signals from FcepsilonRI engagement attenuate mast cell functions

80%

Molfetta R. , Peruzzi G. , Santoni A. , Paolini R.

Archivum Immunologiae et Therapiae Experimentalis

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2007

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tom 55

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nr 4

8

Crosstalk between G protein-coupled receptors and tyrosine kinase signalling; Src take centre stage

80%

Ptasznik A. , Gewirtz A. M.

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nr 1

9

Structure and functions of plant calcium-dependent protein kinases

70%

Klimecka M. , Muszyńska G.

Acta Biochimica Polonica

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2007

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tom 54

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nr 2

219-233

EN

Calcium ions as second messengers play an essential role in many important cellular processes. In plants, transient changes in calcium content in the cytosol (calcium signatures) have been observed during growth, development and under stress conditions. Such diverse functions require many different calcium sensors. One of the largest and most differentiated group of calcium sensors are protein kinases, among them calcium-dependent protein kinases (CDPKs) which were identified only in plants and protists. CDPKs have a regulatory domain which is able to bind calcium ions. For regulation of CDPKs activities not only calcium ions but also specific phospholipids and autophosphorylation are responsible. CDPKs have many different substrates, which reflects the diversity of their functions. Potential protein substrates of CDPK are involved in carbon and nitrogen metabolism, phospholipid synthesis, defense responses, ion and water transport, cytoskeleton organization, transcription and hormone responses. Presently, participation of CDPKs in stress signal transduction pathways (e.g., cold, drought, high salinity, wounding) is intensively studied in many laboratories. An intriguing, but still not fully clarified problem is the cross-talk via CDPKs among different signaling pathways that enables signal integration at different levels and ensure appropriate downstream responses.

10

Differential regulation of signalling pathways for insulin and insulin-like growth factor I

70%

Lopaczynski W.

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nr 1

EN

The insulin receptor (IR) and the insulin-like growth factor receptor I (IGF-IR) have different functions in cell growth, apoptosis, differentation, and transformation. Although some of these differences may be explained by the relative level of receptor expression and receptor structure (a and b subunits), they may also be attributed to differences in intracellular signals generated by insulin and IGF-I. The presence of hybrid receptors (IR ab subunits and IGF-IR ab subunits) making up the heterotetramers has added a new dimension to our understanding of the functional roles of these receptors. However, to date the results of efforts to understand the differences between these two closely related receptors have indicated mostly similarities. For example, both receptors utilize IRS-1/IRS-2 and Shc as immediate downstream adaptors, leading to activation of the Ras, Raf, ERK kinases and PI-3 kinase pathways. We have used the yeast two hybrid system to identify proteins which bind to the activated IGF-IR but not to the IR. The cytoplasmic domain of the IGF-IR was used to screen a human fetal brain library and two isoforms of the 14-3-3 family were identified. 14-3-3 proteins are a highly conserved family of proteins which have recently been shown to interact with other components of the mitogenic and apoptotic signaling pathways, including Raf, BAD, Bcr/Bcr-Abl, middle-T antigen, Ksr, PKC, PI-3 kinase, ASK1 kinase, and cdc25C phosphatase. We also identified human Grb10, an adaptor protein with SH2 domain associated with the IGF-IR b subunit. Smith's laboratory showed that Grb10 preferentially binds to the IR in intact cells. Using the interaction trap screen (active cytoplasmic domain of the IGF-IR) 55PIK and SOCS-2 proteins were also identified. However, 55PIK and SOCS-2 also interact with the IR in the yeast two hybrid system. These studies raise the possibility that 14-3-3 and Grb10 may play a role in insulin and IGF-I signal transduction and may underlie the observed differences.

11

Peptide micro-arrays for kinase profiling

70%

Schutkowski M. , Reimer U. , Panse S. , Dong L. , Schneider-Mergener J.

Cellular and Molecular Biology Letters

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2003

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tom 08

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nr 2A

12

Heterogeneous nuclear ribonucleoprotein [hnRNP] K protein as a docking platform, and its role in cellular signalling

70%

Ostrowski J.

Cellular and Molecular Biology Letters

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2002

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tom 07

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nr Suppl.

13

On the role of spectrin and spectrin SH3 domain in integrin-induced signalling

70%

Bialkowska K. , Fox J. E. B.

Cellular and Molecular Biology Letters

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2001

|

tom 06

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nr 2

14

Exogenous sphingosine 1-phosphate and sphingosylphosphorylcholine do not stimulate phospholipase D in C6 glioma cells

70%

Dygas A. , Sidorko M. , Bobeszko M. , Baranska J.

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nr 1

EN

In the present study we investigate the effect of exogenous sphingosine, sphingosine 1-phosphate and sphingosylphosphorylcholine on phospholipase D (PLD) activity in glioma C6 cells. The cells were prelabeled with [1-14C]palmitic acid and PLD-mediated synthesis of [14C]phosphatidylethanol was measured. Sphingosine 1-phosphate and sphingosylphosphorylcholine did not stimulate [14C]phosphatidyl-ethanol formation either at low (0.1-10 μM) or high (25-100 μM) concentrations. On the other hand, sphingosine at concentrations of 100-250 μM strongly stimulated PLD activity as compared to the effect of phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), known as a PLD activator. The effect of TPA on PLD is linked to the activation of protein kinase C. The present study also shows that sphingosine additively enhances TPA-mediated PLD activity. This is in contrast to the postulated role of sphingosine as a protein kinase C inhibitor. These results demonstrate that in glioma C6 cells sphingosine not only affects PLD independently of its effect on protein kinase C, but also is unable to block TPA-mediated PLD activity.

15

Signal transduction in human pancreatic cancer: roles of transforming growth factor beta, somatostatin receptors, and other signal intermediates

70%

Li M. , Becnel L. S. , Li W. , Fisher W. E. , Chen C. , Yao Q.

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nr 5

16

Alternative binding modes of proline-rich peptides binding to the GYF domain

70%

Gu W. , Kofler M. , Antes I. , Freund C. , Helms V.

Cellular and Molecular Biology Letters

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2005

|

tom 10

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nr Suppl.2

17

Slowing down aging from within: mechanistic aspects of anti-aging hormetic effects of mild heat stress on human cells.

60%

Suresh I.S Rattan , Gonzalez-Dosal R. , Nielsen E. R. , Kraft D. C. , Weibel J. , Kahns S.

Acta Biochimica Polonica

|

2004

|

tom 51

|

nr 2

481-492

EN

Since aging is primarily the result of a failure of maintenance and repair mechanisms, various approaches are being developed in order to stimulate these pathways and modulate the process of aging. One such approach, termed hormesis, involves challenging cells and organisms by mild stress that often results in anti-aging and life prolonging effects. In a series of experimental studies, we have reported that repeated mild heat stress (RMHS) has anti-aging hormetic effects on growth and various cellular and biochemical characteristics of human skin fibroblasts undergoing aging in vitro. These beneficial effects of repeated challenge include the maintenance of stress protein profile, reduction in the accumulation of oxidatively and glycoxidatively damaged proteins, stimulation of the proteasomal activities for the degradation of abnormal proteins, improved cellular resistance to other stresses, and enhanced levels of cellular antioxidant ability. In order to elucidate the molecular mechanisms of hormetic effects of RMHS, we are now undertaking studies on signal transduction pathways, energy production and utilisation kinetics, and the proteomic analysis of patterns of proteins synthesised and their posttranslational modifications in various types of human cells undergoing cellular aging in vitro. Human applications of hormesis include early intervention and modulation of the aging process to prevent or delay the onset of age-related conditions, such as sarcopenia, Alzheimer's disease, Parkinson's disease, cataracts and osteoporosis.

18

Exploring and manipulating function of microglia in brain pathologies

60%

Kaminska B.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

|

nr 3

EN

Microglia are multifunctional immune cells of the brain executing various functions and rapidly responding to pathological insults. Brain injury, hypoxia, infection or aberrant protein accumulation may lead to chronic infl ammation with a progressive shift in microglia function towards infl ammatory phenotype and accumulation of immune cells. Under pathological conditions, the interplay of extrinsic signals directs microglia towards neuroprotective or detrimental phenotype. Molecular mechanisms of initiation, progression and termination of microglia-initiated infl ammatory responses in the brain, in particular gene networks and signaling pathways are poorly understood. Characterization of the global transcriptome of microglia exposed to infl ammatory or cytoprotective signals and analysis of signalling pathways revealed differences in expression of genes encoding cytokines/ chemokines and transcription regulators. Identifi cation of signalling pathways contributing to discrete microglia phenotypes and discovery of transcription regulators which may serve as “master switches” for induction of an infl ammatory phenotype, will allow to target specifi c functions of microglia. Therapeutic approaches targeting signal transduction in microglia will be discussed. A greater understanding of microglia functions coupled with advances in pharmacology and gene therapy will support development of functionally “engineered” microglia able to convey neuroprotection.

19

Protein phosphatase 2A: Variety of forms and diversity of functions

60%

Lechward K. , Awotunde O. S. , Świątek W. , Muszyńska G.

Acta Biochimica Polonica

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2001

|

tom 48

|

nr 4

921-933

EN

Protein phosphatase 2A (PP2A) comprises a diverse family of phosphoserine-and phosphothreonine-specific phosphatases present in all eukaryotic cells. All forms of PP2A contain a catalytic subunit (PP2Ac) which forms a stable complex with the structural subunit PR65/A. The heterodimer PP2Ac-PR65/A associates with regulatory proteins, termed variable subunits, in order to form trimeric holoenzymes attributed with distinct substrate specificity and targeted to different subcellular compartments. PP2Ac activity can be modulated by reversible phosphorylation on Tyr307 and methylation on C-terminal Leu309. Studies on PP2A have shown that this enzyme may be implicated in the regulation of metabolism, transcription, RNA splicing, translation, differentiation, cell cycle, oncogenic transformation and signal transduction.

20

MPP1-based mechanism of resting state raft organization in the plasma membrane. Is it a general or specialized mechanism in erythroid cells?

60%

Trybus M. , Niemiec L. , Biernatowska A. , Hryniewicz-Jankowska A. , Sikorski A. F.

Folia Histochemica et Cytobiologica

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2019

|

tom 57

|

nr 2