共查询到20条相似文献,搜索用时 15 毫秒
1.
Tang J Wu YM Zhao P Yang XM Jiang JL Chen ZN 《Cellular and molecular life sciences : CMLS》2008,65(18):2933-2942
Mechanism of HAb18G/CD147 underlying the metastasis process of human hepatoma cells has not been determined. In the present
study, we found that integrin α3β1 colocalizes with HAb18G/CD147 in human 7721 hepatoma cells. The enhancing effect of HAb18G/CD147
on adhesion, invasion capacities and matrix metalloproteinases (MMPs) secretion was decreased by integrin α3β1 antibodies
(p<0.01). The expressions of integrin downstream molecules including focal adhesion kinase (FAK), phospho-FAK (p-FAK), paxillin,
and phospho-paxillin (p-paxillin) were increased in human hepatoma cells overexpressing HAb18G/CD147. Deletion of HAb18G/CD147
reduces the quantity of focal adhesions and rearranges cytoskeleton. Wortmannin and LY294002, specific phosphatidylinositol
kinase (PI3K) inhibitors, reversed the effect of HAb18G/CD147 on the regulation of intracellular Ca2+ mobilization, significantly reducing cell adhesion, invasion and MMPs secretion potential (p<0.01). Together, these results suggest that HAb18G/CD147 enhances the invasion and metastatic potentials of human hepatoma
cells via integrin α3β1-mediated FAK-paxillin and FAKPI3K-Ca2+ signal pathways.
Received 5 June 2008; received after revision 16 July 2008; accepted 23 July 2008 相似文献
2.
G. M. C. Janssen P. Schwertman T. A. T. Wanga R. S. Jahangir Tafrechi P. J. A. van den Broek A. K. Raap 《Cellular and molecular life sciences : CMLS》2009,66(4):721-730
Cytoplasmic translation is under sophisticated control but how cells adapt its rate to constitutive loss of mitochondrial
oxidative phosphorylation is unknown. Here we show that translation is repressed in cells with the pathogenic A3243G mtDNA
mutation or in mtDNA-less ρ0 cells by at least two distinct pathways, one transiently targeting elongation factor eEF-2 and the other initiation factor
eIF-2α constitutively. Under conditions of exponential cell growth and mammalian target of rapamycin (mTOR) activation, eEF-2
becomes transiently phosphorylated by an AMP-activated protein kinase (AMPK)-dependent pathway, especially high in mutant
cells. Independent of AMPK and mTOR, eIF-2α is constitutively phosphorylated in mutant cells, likely a signature of endoplasmic
reticulum (ER)-stress response induced by the loss of oxidative phosphorylation. While the AMPK/eEF-2K/eEF-2 pathway appears
to function in adaptation to physiological fluctuations in ATP levels in the mutant cells, the ER stress signified by constitutive
protein synthesis inhibition through eIF-2α-mediated repression of translation initiation may have pathobiochemical consequences.
Received 29 October 2008; received after revision 11 December 2008; accepted 16 December 2008 相似文献
3.
A. Deshmukh F. Salehzadeh S. Metayer-Coustard R. Fahlman K. S. Nair L. Al-Khalili 《Cellular and molecular life sciences : CMLS》2009,66(8):1457-1466
Excessive nutrients, especially amino acids, impair insulin action on glucose metabolism in skeletal muscle. We tested the
hypothesis that the branched-chain amino acid leucine reduces acute insulin action in primary myotubes via a negative feedback mechanism involving ribosomal protein S6 kinase 1 (S6K1). The effect of S6K1 on glucose metabolism was
determined by applying RNA interference (siRNA). Leucine (5 mM) reduced glucose uptake and incorporation to glycogen by 13%
and 22%, respectively, compared to the scramble siRNA-transfected control at the basal level. Leucine also reduced insulin-stimulated
Akt phosphorylation, glucose uptake and glucose incorporation to glycogen (39%, 39% and 37%, respectively), and this reduction
was restored after S6K1 silencing. Depletion of S6K1 enhanced basal glucose utilization and protected against the development
of impaired insulin action, in response to excessive leucine. In conclusion, S6K1 plays an important role in the regulation
of insulin action on glucose metabolism in skeletal muscle.
Received 22 December 2008; received after revision 19 February 2009; accepted 23 February 2009 相似文献
4.
Studies of the last two decades have demonstrated that sphingolipids are important signalling molecules exerting key roles
in the control of fundamental biological processes including proliferation, differentiation, motility and survival. Here we
review the role of bioactive sphingolipids such as ceramide, sphingosine, sphingosine 1-phosphate, ganglioside GM3, in the
regulation of skeletal muscle biology. The emerging picture is in favour of a complex role of these molecules, which appear
implicated in the activation of muscle resident stem cells, their proliferation and differentiation, finalized at skeletal
muscle regeneration. Moreover, they are involved in the regulation of contractile properties, tissue responsiveness to insulin
and muscle fiber trophism. Hopefully, this article will provide a framework for future investigation into the field, aimed
at establishing whether altered sphingolipid metabolism is implicated in the onset of skeletal muscle diseases and identifying
new pharmacological targets for the therapy of multiple illnesses, including muscular dystrophies and diabetes.
Received 30 April 2008; received after revision 19 June 2008; accepted 14 July 2008 相似文献
5.
B. Schäfer C. Götz J. Dudek A. Hessenauer U. Matti M. Montenarh 《Cellular and molecular life sciences : CMLS》2009,66(2):339-349
Protein kinase CK2 is a highly conserved serine/threonine kinase that is ubiquitously expressed in eukaryotic cells. CK2 is
a constitutively active tetrameric enzyme composed of two catalytic α and/or α’-subunits and two regulatory β-subunits. There
is increasing evidence that the individual subunits may have independent functions and that they are asymmetrically distributed
inside the cell. To gain a better understanding of the functions of the individual subunits, we employed a yeast-two-hybrid
screen with CK2α and CK2α’. We identified the motor neuron protein KIF5C as a new binding partner for CK2. The interaction
found in the yeast-two-hybrid screen was confirmed by co-sedimentation analysis on a sucrose density gradient and by co-immunoprecipitation
analysis. Pull-down experiments and surface plasmon resonance spectrometry revealed a direct binding of KIF5C to CK2α’. Co-localization
studies with neuroblastoma cells, bone marrow and with primary neurons confirmed the biochemical analysis that KIF5C preferentially
bound to CK2α’.
Received 8 August 2008; received after revision 3 November 2008; accepted 4 November 2008 相似文献
6.
Muñoz U Bartolomé F Esteras N Bermejo-Pareja F Martín-Requero A 《Cellular and molecular life sciences : CMLS》2008,65(21):3507-3519
It has been proposed that neuroinflammation, among other factors, may trigger an aberrant neuronal cell cycle re-entry leading
to neuronal death. Cell cycle disturbances are also detectable in peripheral cells from Alzheimer’s disease (AD) patients.
We previously reported that the anti-inflammatory 15- deoxy-Δ12,14-prostaglandin J
2 (15d-PGJ
2) increased the cellular content of the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This work
aimed at elucidating the mechanisms of 15d-PGJ
2-induced p27 accumulation. Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein were altered by 15d-PGJ2
by mechanisms dependent on PI3K/Akt activity. 15d-PGJ
2 prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by blocking its binding to the 85-kDa regulatory
subunit of PI3K. These effects of 15d-PGJ
2 were not mimicked by 9,10-dihydro-15-deoxy-Δ12,14- prostaglandin J
2, suggesting that 15d-PGJ
2 acts independently of peroxisome proliferator-activated receptor γ activation and that the α,β-unsaturated carbonyl group
in the cyclopentenone ring of 15d-PGJ
2 is a requisite for the observed effects.
Received 14 July 2008; received after revision 2 September 2008; accepted 12 September 2008 相似文献
7.
Mitochondrial dysfunction and protein kinase C (PKC) activation are consistently found in diabetic cardiomyopathy but their
relationship remains unclear. This study identified mitochondrial aconitase as a downstream target of PKC activation using
immunoblotting and mass spectrometry, and then characterized phosphorylation-induced changes in its activity in hearts from
type 1 diabetic rats. PKCβ2 co-immunoprecipitated with phosphorylated aconitase from mitochondria isolated from diabetic hearts. Augmented phosphorylation
of mitochondrial aconitase in diabetic hearts was found to be associated with an increase in its reverse activity (isocitrate
to aconitate), while the rate of the forward activity was unchanged. Similar results were obtained on phosphorylation of mitochondrial
aconitase by PKCβ2 in vitro. These results demonstrate the regulation of mitochondrial aconitase activity by PKC-dependent phosphorylation. This may
influence the activity of the tricarboxylic acid cycle, and contribute to impaired mitochondrial function and energy metabolism
in diabetic hearts.
Received 31 October 2008; received after revision 17 December 2008; accepted 2 January 2009 相似文献
8.
The identification of the aspartic protease BACE1 (β-secretase) was a defining event in research aimed at understanding the
molecular mechanisms that underlie Alzheimer’s disease (AD) pathogenesis. This is because BACE1 catalyses the rate limiting
step in the production of amyloid-β (Aβ) the principal component of plaque pathology in AD, the excessive production of which
is believed to be a primary cause of neurodegeneration, and cognitive dysfunction in AD. Subsequent discoveries showed that
genetic deletion of BACE1 completely abolishes Aβ production and deposition in vivo, and that BACE1 activity is significantly increased in AD brain. In this review we present current knowledge on BACE1, discussing
its structure, function and complex regulation with a view to understanding BACE1 function in the brain, and BACE1 as a target
in blocking aberrant Aβ production in AD.
Received 15 May 2008; received after revision 13 June 2008; accepted 18 June 2008 相似文献
9.
Sampaio MS Bezerra IP Peçanha FL Fonseca PH Capella MA Lopes AG 《Cellular and molecular life sciences : CMLS》2008,65(19):3093-3099
The lack of Na+,K+-ATPase expression in intercalated cells (IC) is an intriguing condition due to its fundamental role in cellular homeostasis.
In order to better understand this question we compared the activities of Na+,K+-ATPase and Na+-ATPase in two MDCK cell clones: the C11, with IC characteristics, and the C7, with principal cells (PC) characteristics.
The Na+,K+-ATPase activity found in C11 cells is far lower than in C7 cells and the expression of its β-subunit is similar in both cells.
On the other hand, a subset of C11 without α-subunit expression has been found. In C11 cells the Na+-ATPase activity is higher than that of the Na+,K+-ATPase, and it is increased by medium alkalinization, suggesting that it could account for the cellular Na+-homeostasis. Although further studies are necessary for a better understanding of these findings, the presence of Na+-ATPase may explain the adequate survival of cells that lack Na+,K+-ATPase.
Received 09 July 2008; received after revision 03 August 2008; accepted 12 August 2008 相似文献
10.
D. E. Dye S. Karlen B. Rohrbach O. Staub L. R. Braathen K. A. Eidne D. R. Coombe 《Cellular and molecular life sciences : CMLS》2009,66(4):681-696
hShroom1 (hShrm1) is a member of the Apx/Shroom (Shrm) protein family and was identified from a yeast two-hybrid screen as
a protein that interacts with the cytoplasmic domain of melanoma cell adhesion molecule (MCAM). The characteristic signature
of the Shrm family is the presence of a unique domain, ASD2 (Apx/Shroom domain 2). mRNA analysis suggests that hShrm1 is expressed
in brain, heart, skeletal muscle, colon, small intestine, kidney, placenta and lung tissue, as well a variety of melanoma
and other cell lines. Co-immunoprecipitation and bioluminescence resonance energy transfer (BRET) experiments indicate that
hShrm1 and MCAM interact in vivo and by immunofluorescence microscopy some co-localization of these proteins is observed. hShrm1 partly co-localises with
β-actin and is found in the Triton X-100 insoluble fraction of melanoma cell extracts. We propose that hShrm1 is involved
in linking MCAM to the cytoskeleton.
D. E. Dye, S. Karlen: These authors contributed equally to this work.
Received 09 October 2008; received after revision 23 November 2008; accepted 09 December 2008 相似文献
11.
Diego-García E Abdel-Mottaleb Y Schwartz EF de la Vega RC Tytgat J Possani LD 《Cellular and molecular life sciences : CMLS》2008,65(1):187-200
Among the scorpion venom components whose function are poorly known or even show contrasting pharmacological results are those
called “orphan peptides”. The most widely distributed are named β-KTx or scorpine-like peptides. They contain three disulfide
bridges with two recognizable domains: a freely moving N-terminal amino acid sequence and a tightly folded C-terminal region
with a cysteine-stabilized α/β (CS-αβ) motif. Four such peptides and three cloned genes are reported here. They were assayed
for their cytolytic, antimicrobial and K
+ channel-blocking activities. Two main characteristics were found: the existence of an unusual structural and functional diversity,
whereby the full-length peptide can lyse cells or kill microorganisms, and a C-terminal domain containing the CS-αβ motif
that can block K
+ channels. Furthermore, sequence analyses and phylogenetic reconstructions are used to discuss the evolution of this type
of peptide and to highlight the versatility of the CS-αβ structures.
Received 13 August 2007; received after revision 30 October 2007; accepted 2 November 2007 相似文献
12.
S. M. Houten M. Chegary H. te Brinke W. J. Wijnen J. F. C. Glatz J. J. F. P. Luiken F. A. Wijburg R. J. A. Wanders 《Cellular and molecular life sciences : CMLS》2009,66(7):1283-1294
Organs are flexible as to which substrates they will use to maintain energy homeostasis. Under well-fed conditions, glucose
is a preferred substrate for oxidation. During fasting, fatty acid oxidation will become a more important energy source. Glucose
oxidation is decreased by fatty acids, a process in which the pyruvate dehydrogenase complex (PDH) and its regulator pyruvate
dehydrogenase kinase 4 (PDK4) play important roles. It is currently unknown how energy status influences PDH activity. We
show that AMP-activated protein kinase (AMPK) activation by hypoxia and AICAR treatment combined with fatty acid administration
synergistically induce PDK4 expression. We provide evidence that AMPK activation modulates ligand-dependent activation of
peroxisome proliferator-activated receptor. Finally, we show that this synergistic induction of PDK4 decreases cellular glucose
oxidation. In conclusion, AMPK and fatty acids play a direct role in fuel selection in response to cellular energy status
in order to spare glucose.
S. M. Houten, M. Chegary: These two authors contributed equally to this work.
Received 11 July 2008; received after revision 26 January 2009; accepted 02 February 2009 相似文献
13.
E. Cohen-Hillel R. Mintz T. Meshel B.-Z. Garty A. Ben-Baruch 《Cellular and molecular life sciences : CMLS》2009,66(5):884-899
The chemokine CXCL8 is a powerful inducer of directional cell motility, primarily during inflammation. In this study, we found
that CXCL8 stimulation led to paxillin phosphorylation in normal neutrophils, and that both CXCL8 receptors (CXCR1 and CXCR2)
mediated CXCL8-induced paxillin phosphorylation. In CXCR2-transfected cells, the process depended on Gαi and Gαs coupling to CXCR2. Dominant negative (DN) paxillin increased CXCL8-induced adhesion and migration, indicating that endogenous
paxillin keeps migration at submaximal levels. Furthermore, using activating antibodies to β1 integrins, analyses with focal
adhesion kinase (FAK) DN variant (FRNK) and co-immunoprecipitations of FAK and paxillin, we found that β1 integrin ligation
cooperates with CXCL8-induced stimulation, leading to FAK activation and thereafter to FAK-mediated paxillin phosphorylation.
Our findings indicate that paxillin keeps directional motility at a restrained magnitude, and suggest that perturbations in
its activation may lead to chemotactic imbalance and to pathological conditions associated with excessive or reduced leukocyte
migration.
R. Mintz, T. Meshel: These authors contributed equally to this work.
Received 31 July 2008; received after revision 14 December 2008; accepted 16 December 2008 相似文献
14.
Moorwood C 《Cellular and molecular life sciences : CMLS》2008,65(19):2957-2963
Syncoilin is a member of the intermediate filament protein family, highly expressed in skeletal and cardiac muscle. Syncoilin
binds α-dystrobrevin, a component of the dystrophin associated protein complex (DAPC) located at the muscle cell membrane,
and desmin, a muscle-specific intermediate filament protein, thus providing a link between the DAPC and the muscle intermediate
filament network. This link may be important for muscle integrity and force transduction during contraction, a theory that
is supported by the reduced force-generating capacity of muscles from syncoilin-null mice. Additionally, syncoilin is found
at increased levels in the regenerating muscle fibres of patients with muscular dystrophies and mouse models of muscle disease.
Therefore, syncoilin may be important for muscle regeneration in response to injury. The aims of this article are to review
current knowledge about syncoilin and to discuss its possible functions in skeletal muscle.
Received 21 May 2008; received after revision 10 July 2008; accepted 18 July 2008 相似文献
15.
The continuing disappearance of “pure” Ca2+ buffers 总被引:1,自引:1,他引:0
B. Schwaller 《Cellular and molecular life sciences : CMLS》2009,66(2):275-300
Advances in the understanding of a class of Ca2+-binding proteins usually referred to as “Ca2+ buffers” are reported. Proteins historically embraced within this group include parvalbumins (α and β), calbindin-D9k, calbindin-D28k
and calretinin. Within the last few years a wealth of data has accumulated that allow a better understanding of the functions
of particular family members of the >240 identified EF-hand Ca2+-binding proteins encoded by the human genome. Studies often involving transgenic animal models have revealed that they exert
their specific functions within an intricate network consisting of many proteins and cellular mechanisms involved in Ca2+ signaling and Ca2+ homeostasis, and are thus an essential part of the Ca2+ homeostasome. Recent results indicate that calbindin-D28k, possibly also calretinin and oncomodulin, the mammalian β parvalbumin,
might have additional Ca2+ sensor functions, leaving parvalbumin and calbindin-D9k as the only “pure” Ca2+ buffers.
Received 10 September 2008; received after revision 15 October 2008; accepted 4 November 2008 相似文献
16.
Action of juvenile hormone on the follicle cells ofRhodnius prolixus: Evidence for a novel regulatory mechanism involving protein kinase C 总被引:1,自引:0,他引:1
Summary Juvenile hormone (JH) is known to act on the membranes of the follicle cells ofRhodnius, activating a specific Na+, K+-ATPase. This leads to a decrease in volume of the cells and the appearance of spaces between them (patency). The addition of an inhibitor of protein kinase C, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), to the medium in vitro inhibits the action of JH on the follicle cells. PDBU (phorbol-12,13-dibutyrate) mimics the action of JH in vitro and the response of the follicle cells to, PDBU is blocked by ouabain. It is concluded that the activation of protein kinase C is a required step in the chain of events leading to activation of the JH-dependent ATPase and set in train by the binding of JH to the membrane. 相似文献
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19.
G. Bailin 《Cellular and molecular life sciences : CMLS》1984,40(11):1185-1188
Summary In smooth muscle the Mr 20,000 light chain of myosin is phosphorylated by a calmodulin-dependent protein kinase. It consists of 2 subunits: calmodulin, an acidic protein of Mr 17,000 that binds 4 moles of Ca2+; and a larger protein of Mr circa 130,000. Activation of the kinase is dependent upon their association in the presence of Ca2+. Cyclic AMP-dependent protein kinase phosphorylation of the myosin light chain kinase occurs at 2 sites. It decreases the affinity of the kinase for calmodulin and a reduction in the rate of light chain phosphorylation occurs. The kinase has an overall asymmetric shape composed of a globular head and tail region for the skeletal muscle enzyme. Trypsin digestion of this kinase releases a fragment of Mr 36,000 from the globular region that contains the catalytic and calmodulin binding sites. Chymotrypsin digestion of the kinase from smooth muscle generates a fragment of Mr 80,000 that does not contain the calmodulin binding or cyclic AMP-dependent protein kinase phosphorylation sites. It is a Ca2+-independent form of the kinase that phosphorylates the light chain of myosin. These structural features indicate a regulatory role for the kinase in smooth muscle phosphorylation and contraction. 相似文献
20.
Dong Gao Ruipeng Wang Bingfeng Li Yongkang Yang Zhonghe Zhai Dan-Ying Chen 《Cellular and molecular life sciences : CMLS》2009,66(15):2573-2584
Toll-like receptors (TLRs) act as sensors of microbial components and elicit innate immune responses. All TLR signaling pathways
activate the nuclear factor-kappaB (NF-κB), which controls the expression of inflammatory cytokine genes. Transforming growth
factor-β-activated kinase 1 (TAK1) is a serine/threonine protein kinase that is critically involved in the activation of NF-κB
by tumor necrosis factor (TNFα), interleukin-1β (IL-1β) and TLR ligands. In this study, we identified a novel protein, WD40
domain repeat protein 34 (WDR34) as a TAK1-interacting protein in yeast two-hybrid screens. WDR34 interacted with TAK1, TAK1-binding
protein 2 (TAB2), TAK1-binding protein 3 (TAB3) and tumor necrosis factor receptor-associated factor 6 (TRAF6) in overexpression
and under physiological conditions. Overexpression of WDR34 inhibited IL-1β-, polyI:C- and lipopolysaccharide (LPS)-induced
but not TNFα-induced NF-κB activation, whereas knockdown of WDR34 by a RNA-interference construct potentiated NF-κB activation
by these ligands. Our findings suggest that WDR34 is a TAK1-associated inhibitor of the IL-1R/TLR3/TLR4-induced NF-κB activation
pathway.
D. Gao and R. Wang contributed equally to this work. 相似文献