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1.
Sánchez-Margalet V González-Yanes C Santos-Alvarez J Najib S 《Cellular and molecular life sciences : CMLS》1999,55(1):142-147
Insulin action is initiated by binding to its cognate receptor, which then triggers multiple cellular responses by activating
different signaling pathways. There is evidence that insulin receptor signaling may involve G protein activation in different
target cells. We have studied the activation of G proteins in rat hepatoma (HTC) cells. We found that insulin stimulated binding
of guanosine 5′-O-(3-thiotriphosphate) (GTP-γ-35S) to plasma membrane proteins of HTC cells, in a dose-dependent manner. This effect was completely blocked by pertussis toxin
treatment of the membranes, suggesting the involvement of G proteins of the Gα
i/Gα
o family. The expression of these Gα proteins was checked by Western blotting. Next, we used blocking antibodies to sort out the specific Gα protein activated by insulin stimulation. Anti-Gα
il,2 antibodies completely prevented insulin-stimulated GTP binding, whereas anti-Gα
o,i3 did not modify this effect of insulin on GTP binding. Moreover, we found physical association of the insulin receptor with
Gα
i1,2 by copurification studies. These results further support the involvement of a pertussis toxin-sensitive G protein in insulin
receptor signaling and provides some evidence of specific association and activation of Gα
i1,2 protein by insulin. These findings suggest that Gα
i1,2 proteins might be involved in insulin action.
Received 23 September 1998; received after revision 23 November 1998; accepted 25 November 1998 相似文献
2.
Ligand recognition by the I domain-containing integrins 总被引:11,自引:0,他引:11
Seven of the integrin α subunits described to date, α
1 , α
2 , α
L , α
X , α
d , α
M and α
E , contain a highly conserved I (or A) domain of approximately 200 amino acid residues inserted near the amino-terminus of
the subunit. As the result of a variety of independent experimental approaches, a large body of data has recently accumulated
that indicates that the I domains are independent, autonomously folding domains capable of directly binding ligands that play
a necessary and important role in ligand binding by the intact integrins. Recent crystallographic studies have elucidated
the structures of recombinant α
M and α
L I domains and also delineated a novel divalent cation-binding motif within the I domains (metal ion-dependent adhesion site,
MIDAS) that appears to mediate the divalent cation binding of the I domains and the I domain-containing integrins to their
ligands. 相似文献
3.
Signal regulation by family conspiracy 总被引:6,自引:0,他引:6
The signal regulating proteins (SIRPs) are a family of ubiquitously expressed transmembrane glycoproteins composed of two
subgroups: SIRPα and SIRPβ, containing more than ten members. SIRPα has been shown to inhibit signalling through a variety of receptors including receptor tyrosine kinases and cytokine receptors.
This function involves protein tyrosine kinases and is dependent on immunoreceptor tyrosine-based inhibition motifs which
recruit key protein tyrosine phosphatases to the membrane. Negative regulation by SIRPα may also involve its ligand, CD47, in a bi-directional signalling mechanism. The SIRPβ subtype has no cytoplasmic domain but instead associates with at least one other transmembrane protein (DAP-12, or KARAP).
DAP-12 possesses immunoreceptor tyrosine-based activation motifs within its cytoplasmic domain that are thought to link SIRPβ to activating machinery. SIRPα and SIRPβ thus have complementary roles in signal regulation and may conspire to tune the response to a stimulus.
Received 6 July 2000; revised 2 August 2000; accepted 5 August 2000 相似文献
4.
Until recently, the expression and primary function of the cell surface receptor CD40 and its ligand CD154 were considered
restricted to B and T lymphocytes, and their interactions required for the thymus-dependent humoral response. However, current
work from several groups challenges this view of the CD40/CD154 dyad as a mere mediator of lymphocyte communication. A variety
of non-lymphocytic cell types express both receptor and ligand, including hematopoetic and non-hematopoetic cells, such as
monocytes, basophils, eosinophils, dendritic cells, fibroblasts, smooth muscle, and endothelial cells. Accordingly, ligation
of CD40 mediates a broad variety of immune and inflammatory responses, such as the expression of adhesion molecules, cytokines,
matrix-degrading enzymes, prothrombotic activities, and apoptotic mediators. Consequently, CD40 signaling has been associated
with pathogenic processes of chronic inflammatory diseases, such as autoimmune diseases, neurodegenerative disorders, graft-versus-host
disease, cancer, and atherosclerosis. This review focuses on the synthesis and structure of CD40 and outlines CD154/CD40 signaling
pathways, and emphasizes the previously unexpected importance of the CD40/CD154 receptor/ligand dyad in a spectrum of immunoregulatory
processes and prevalent human diseases.
Received 10 January 2000; revised 16 June 2000; accepted 5 July 2000
RID="†"
ID="†" Review
RID="*"
ID="*" Corresponding author. 相似文献
5.
Integrins and cardiovascular disease 总被引:2,自引:0,他引:2
Cardiovascular diseases involve abnormal cell-cell interactions leading to the development of atherosclerotic plaque, which
when ruptured causes massive platelet activation and thrombus formation. Parts of a loose thrombus may detach to form an embolus,
blocking circulation at a more distant point. The integrins are a family of adhesive cell receptors interacting with adhesive
proteins or with counterreceptors on other cells. There is now solid evidence that the major integrin on platelets, the fibrinogen
receptor α
IIb
β
3 , has an important role in several aspects of cardiovascular diseases and that its regulated inhibition leads to a reduction
in incidence and mortality due to these disorders. The development of α
IIb
β
3 inhibitors is an important strategy of many pharmaceutical companies which foresee a large market for the treatment of acute
conditions in surgery, the symptoms of chronic conditions and, it is hoped, maybe even the successful prophylaxis of these
conditions. Although all the associated problems have not been solved, the undoubted improvements in patient care resulting
from the first of these treatments in the clinic have stimulated further research on the role of integrins on other vascular
cells in these processes and in the search for new inhibitors. Both the development of specific inhibitors and of mice with
specific integrin subunit genes ablated have contributed to a better understanding of the function of integrins in development
of the cardiovascular system. 相似文献
6.
Nakashima K Nishino A Horikawa Y Hirose E Sugiyama J Satoh N 《Cellular and molecular life sciences : CMLS》2011,68(9):1623-1631
The native form of cellulose is a fibrillar composite of two crystalline phases, the triclinic Iα and monoclinic Iβ allomorphs. Allomorph ratios are species-specific, and this gives rise to natural structural variations in cellulose crystals.
However, the mechanisms contributing to crystal formation remain unknown. We show that the two crystalline phases of cellulose
are tailored to distinct structures during different developmental stages of the tunicate chordate Oikopleura dioica. Larval cellulose consisting of Iα allomorph constitutes the body cuticle fin, whereas adult cellulose consisting of Iβ allomorph frames a mucous filter-feeding device, the “house.” Both structures are secreted from the epidermis in accordance
with the mutually exclusive expression patterns of two distinct putative cellulose synthase genes. We discuss a possible linkage
between structural variations of the crystalline phases of cellulose and the underlying evolutionary genetics of cellulose
biosynthesis. 相似文献
7.
Allometry of mammalian cellular oxygen consumption 总被引:3,自引:0,他引:3
R.K. Porter 《Cellular and molecular life sciences : CMLS》2001,58(5-6):815-822
In the 1930s, Max Kleiber and Samuel Brody established that the interspecies correlation between mammalian body mass and
metabolic rate (αM0.75) cannot be explained (solely) by whole body surface area (αM0.66) to volume ratios. Metabolic considerations must also be taken into account. Decreases in the proportion of visceral organ
mass to whole body mass can account for some of the whole body metabolic differences. However, superimposed upon these anatomical
differences, the metabolism of tissues and cells has been demonstrated to decrease with increasing body mass. These decreases
in oxygen consumption rates (with increasing body mass) in cells and tissues can be explained by a decrease in ATP turnover
and mitochondrial density and an increase in mitochondrial functional efficiency (decrease in proton leak). The majority of
the proton leak differences reflect differences in mitochondrial inner membrane surface area. Indeed, liver metabolism correlates
directly with liver mitochondrial inner membrane surface area. Apart from being a significant contributor (~25 %) to basal
metabolism, mitochondrial proton leak is a major factor determining the differences in basal metabolism between mammals of
different body mass.
Received 31 May 2000; received after revision 2 October 2000; accepted 14 November 2000 相似文献
8.
Lyme disease is a multisystem illness initiated upon infection with the spirochete Borrelia burgdorferi. Whereas the majority of patients who develop Lyme arthritis may be successfully treated with antibiotic therapy, about 10%
go on to develop arthritis which persists for months to years, despite antibiotic therapy. Development of what we have termed
treatment-resistant Lyme arthritis has previously been associated with both the presence of particular major histocompatibility
complex class II alleles and immunoreactivity to the spriochetal outer surface protein A (OspA). Recently, we showed that
patients with treatment-resistant Lyme arthritis, but not patients with other forms of arthritis, generate synovial fluid
T cell responses to an immunodominant epitope of OspA and a highly homologous region of the human-lymphocyte-function-associated
antigen-1α
L chain. Identification of a bacterial antigen capable of propagating an autoimmune response against a self-antigen provides
a model of molecular mimicry in the pathogenesis of treatment-resistant Lyme arthritis.
Received 21 December 1999; received after revision 10 April 2000; accepted 11 April 2000 相似文献
9.
GPR39 is a vertebrate G protein-coupled receptor related to the ghrelin/neurotensin receptor subfamily. The receptor is expressed
in a range of tissues including the pancreas, gut/gastrointestinal tract, liver, kidney and in some regions of the brain.
GPR39 was initially thought to be the cognitive receptor for the peptide hormone, obestatin. However, subsequent in vitro
studies have failed to demonstrate binding of this peptide to the receptor. Zn2+ has been shown to be a potent stimulator of GPR39 activity via the Gαq, Gα12/13 and Gαs pathways. The potency and specificity of Zn2+ in activating GPR39 suggest it to be a physiologically important agonist. GPR39 is now emerging as an important transducer
of autocrine and paracrine Zn2+ signals, impacting upon cellular processes such as insulin secretion, gastric emptying, neurotransmission and epithelial
repair. This review focuses on the molecular, structural and biological properties of GPR39 and its various physiological
functions. 相似文献
10.
Rana oocytes have previously been shown to contain much more soluble tubulin than does the brain, suggesting different assembly
and disassembly dynamics of frog oocyte tubulin compared to that in brain. By using centrifugation, SDS-PAGE, two-dimensional
gel electrophoresis and Western blots, probed with anti-α-tubulin monoclonal antibodies, polymorphic α-tubulins (isoforms)
were compared in brains and follicle-enclosed oocytes of northern (Rana pipiens) and southern (R. berlandieri) frogs. Oocyte tubulin in both species had isoforms with greater ranges of isoelectric point (pI) than those of brain tubulins;
in particular, the oocyte tubulin pIs ranged further into the acidic region of the isoelectric-focusing gels than corresponding
brain tubulin. This difference may, in part, be responsible for the previously reported assembly differences between oocyte
tubulin (undetectable assembly) and brain tubulin (high assembly). Isoforms of α-tubulin with relat
ively acidic pI were more abundant in northern frog brain and oocyte soluble extracts than in analogous extracts from southern
frogs. Furthermore, additional acidic α-tubulin isoforms were found in progesterone-treated oocytes (i.e., eggs), indicating
increased heterogeneity of acidic a-tubulin isoforms during oocyte meiotic maturation. Among northern frog oocyte soluble
components fractionated on Superose-6b columns, tubulin complexes with apparent molecular mass of about 1800 kDa were found
to contain acidic α-tubulin isoforms while the putative oligomeric tubulins with an apparent molecular mass of about 250 kDa
contained an additional relatively basic α-tubulin isoform. The acidic α-tubulin isoforms, therefore, are proposed to be associated
with cold-adaptable cells of brain and oocytes, and may also be involved in stabilization of large soluble tubulin complexes
in oocytes of the northern frog.
Received 1 October 2002; accepted 9 October 2002
RID="*"
ID="*"Corresponding author. 相似文献
11.
The superoxide-generating NADPH oxidase: structural aspects and activation mechanism 总被引:31,自引:0,他引:31
Vignais PV 《Cellular and molecular life sciences : CMLS》2002,59(9):1428-1459
Flavocytochrome b
558
is the catalytic core of the respiratory-burst oxidase, an enzyme complex that catalyzes the NADPH-dependent reduction of
O2 into the superoxide anion O2
- in phagocytic cells. Flavocytochrome b
558
is anchored in the plasma membrane. It is a heterodimer that consists of a large glycoprotein gp91phox (phox for phagocyte oxidase) (β subunit) and a small protein p22phox (α subunit). The other components of the respiratory-burst oxidase are water-soluble
proteins of cytosolic origin, namely p67phox, p47phox, p40phox and Rac. Upon cell stimulation, they assemble with the membrane-bound
flavocytochrome b
558
which becomes activated and generates O2
-. A defect in any of the genes encoding gp91phox, p22phox, p67phox or p47phox results in chronic granulomatous disease, a
genetic disorder characterized by severe and recurrent infections, illustrating the role of O2
- and the derived metabolites H2O2 and HOCl in host defense against invading microorganisms. The electron carriers, FAD and hemes b, and the binding site for NADPH are confined to the gp91phox subunit of flavocytochrome b
558
. The p22phox subunit serves as a docking site for the cytosolic phox proteins. This review provides an overview of current
knowledge on the structural organization of the O2
--generating flavocytochrome b
558
, its kinetics, its mechanism of activation and the regulation of its biosynthesis. Homologues of gp91phox, called Nox and
Duox, are present in a large variety of non-phagocytic cells. They exhibit modest O2
--generating oxidase activity, and some act as proton channels. Their role in various aspects of signal transduction is currently
under investigation and is briefly discussed.
Received 28 May 2002; received after revision 20 June 2002; accepted 24 June 2002 相似文献
12.
Structure and assembly of the 20S proteasome 总被引:3,自引:0,他引:3
W. L. H. Gerards W. W. de Jong W. Boelens H. Bloemendal 《Cellular and molecular life sciences : CMLS》1998,54(3):253-262
The barrel-shaped 20S proteasome is one of the two components of a larger 26S particle, the multicatalytic 2000-kDa protease
complex. The proteolytic sites are located in the inner chamber of the 20S particle and are only accessible via narrow entrances.
This paper reviews the current knowledge concerning proteasome formation, proteolytic activities, structural aspects and assembly.
Eukaryotic proteasomes are made up by four rings each of which contains seven different subunits occurring at fixed positions.
While the outer rings contain α-type subunits, the inner ones comprise β-type subunits. The current assembly model for eukaryotic 20S proteasomes is based upon the detection of 13S and 16S intermediates,
respectively, in addition to previous findings with archaebacterial and eubacterial proteasome assembly. The available data
suggest a cooperative assembly of the α-type and β-type subunits into half proteasome-like complexes followed by dimerization into proteasomes. During or after dimerization
of half proteasomes, the β-type subunits are processed. The prosequence of the β-type subunits is essential for the assembly process and prevents protease activity of immature proteasomes. 相似文献
13.
Summary Using two independent techniques, ultracentrifugation in a KBr-gradient, and native pore polyacrylamide gel electrophoresis in combination with [3H]-epoxyfarnesyldiazoacetate photoaffinity labeling, we showed that in the hemolymph ofPeriplaneta americana, and probably also inLeptinotarsa decemlineata JH-III binds to the lipophorin, whereas inLocusta migratoria JH-III binds to a different protein. 相似文献
14.
4-Hydroxynonenal-modified amyloid-beta peptide inhibits the proteasome: possible importance in Alzheimer's disease 总被引:3,自引:0,他引:3
Shringarpure R Grune T Sitte N Davies KJ 《Cellular and molecular life sciences : CMLS》2000,57(12):1802-1809
The amyloid β-peptide (Aβ) is a 4-kDa species derived from the amyloid precursor protein, which accumulates in the brains of patients with Alzheimer’s
disease. Although we lack full understanding of the etiology and pathogenesis of selective neuron death, considerable data
do imply roles for both the toxic Aβ and increased oxidative stress. Another significant observation is the accumulation of abnormal, ubiquitin-conjugated proteins
in affected neurons, suggesting dysfunction of the proteasome proteolytic system in these cells. Recent reports have indicated
that Aβ can bind and inhibit the proteasome, the major cytoslic protease for degrading damaged and ubiquitin-conjugated proteins.
Earlier results from our laboratory showed that moderately oxidized proteins are preferentially recognized and degraded by
the proteasome; however, severely oxidized proteins cannot be easily degraded and, instead, inhibit the proteasome. We hypothesized
that oxidatively modified Aβ might have a stronger (or weaker) inhibitory effect on the proteasome than does native Aβ. We therefore also investigated the proteasome inhibitory action of Aβ
1–40 (a peptide comprising the first 40 residues of Aβ) modified by the intracellular oxidant hydrogen peroxide, and by the lipid peroxidation product 4-hydroxynonenal (HNE). H2O2 modification of Aβ
1–40 generates a progressively poorer inhibitor of the purified human 20S proteasome. In contrast, HNE modification of Aβ
1–40 generates a progressively more selective and efficient inhibitor of the degradation of fluorogenic peptides and oxidized
protein substrates by human 20S proteasome. This interaction may contribute to certain pathological manifestations of Alzheimer’s
disease
Received 26 September 2000; accepted 26 September 2000 相似文献
15.
A new hemagglutinin was isolated from the plasmodium ofPhysarum polycephalum by salting out with ammonium sulphate followed by chromatography on DE-32, DEAE-Toyopearl and hydroxyapatite. This hemagglutinin, named physarumin, was purified 1000-fold over crude extracts. The molecular weight of physarumin was determined to be 22,000 by size exclusion chromatography on Bio-Gel P-60 and 8,700 by SDS-polyacrylamide gel electrophoresis. Physarumin agglutinated rabbit, guinea pig, horse and human erythrocytes. Physarumin-induced hemagglutination was inhibited by fetuin and 1 glycoprotein, but not by commercially available mono-and disaccharides. Hemagglutinating activity was blocked by EDTA, and was restored by adding Ca2+ but not by Mg2+. 相似文献
16.
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
17.
Franciosi S 《Cellular and molecular life sciences : CMLS》2001,58(7):921-930
α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors are one type of ionotropic glutamate receptor involved
in rapid excitatory synaptic transmission. AMPA receptors have been increasingly implicated in long-term potentiation, and
recent evidence suggests that they may play a role in disorders affecting the nervous system. The finding that early in postnatal
development AMPA receptors are not expressed has lately been the focus of much attention. Resolving the factors involved in
AMPA receptor expression suggests that their induction is a developmentally regulated process with the possibility that alterations
in receptor expression may be correlated with pathology in neurological disorders. This paper provides an overview of factors
involved in AMPA receptor induction as well as of their role in plasticity and neuronal pathologies.
Received 5 December 2000; received after revision 12 January 2001; accepted 2 February 2001 相似文献
18.
M. Capdevila N. Cols N. Romero-Isart R. Gonzàlez-Duarte S. Atrian P. Gonzàlez-Duarte 《Cellular and molecular life sciences : CMLS》1997,53(8):681-688
Genetic engineering, coupled with spectro scopic analyses, has enabled the metal binding proper ties of the α and β subunits of mouse metallothionein 1 (MT) to be characterized. A heterologous expression system in E.coli has led to high yields of their pure zinc-complexed forms. The cadmium(II) binding properties of recombinant Zn4-αMT and Zn3-βMT have been studied by electronic absorption and circular dichroism. The former binds Cd(II) identically to α fragments obtained from mammalian organs, showing that the recombinant polypeptide behaves like the na tive protein. Titration
of Zn3-βMT with CdCl2 results in the formation of Cd3-βMT. The addition of excess Cd(II) leads to Cd4-βMT which, with the extra loading of Cd(II), unravels to give rise isodichroically to Cd9-βMT. The effect of cadmium-displaced Zn(II) ions and excess Cd(II) above the full metal occupancy of three has been studied
using Chelex-100. The Cd3-βMT species is stable in the presence of this strong metal-chelating agent.
Received 20 May 1997; received after revision 7 July 1997; accepted 9 July 1997 相似文献
19.
T. Matsuoka T. Nishizaki Y. Ikeuchi Y. Okada K. Sumino 《Cellular and molecular life sciences : CMLS》1997,53(3):233-236
Effects of serotonin (5-HT) on cerebral cortical neurons were examined by patch clamp techniques. 5-HT produced a variety
of responses such as outward (19/73 patches/neurons), slow inward (15/73 patches/neurons), fast inward (8/73 patches/neurons),
and mixed currents (initially fast inward deflection followed by an outward response: 2/73 patches/neurons), with a latency
of 12 sec, 15 sec, 0 sec, and 0 sec respectively, at a holding potential of −60 mV in whole-cell patches. The fast inward
currents were again evoked by a selective 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide hydrochloride (CPBG). In the
cell-attached patch clamp configuration, 5-HT inside the patch pipette elicited single channel currents with slope conductances
of 42 pS and 132 pS (4/42 patches/neurons). CPBG inside the patch pipette evoked inward single channel currents with a lower
slope conductance of 41 pS (3/23 patches/neurons). In contrast, application of 5-HT or a 5-HT2 receptor agonist, α-methyl-5-hydroxytryptamine-maleate, outside the patch pipette induced outward single channel currents with a major slope
conductance of 140 pS (8/30 patches/neurons) or 135 pS (6/20 patches/neurons), respectively. These results indicate that the
outward and fast inward currents may be mediated respectively by the 5-HT2 receptor, which is coupled to a G-protein, and by the 5-HT3 receptor, which contains the non-selective cation channel, and that the mixed type may be caused by both the 5-HT2 and 5-HT3 receptors.
Received 27 September 1996; received after revision 4 November 1996; accepted 7 November 1996 相似文献
20.
The central role played by the αIIbβ3 receptor in platelet aggregation, and hence in platelet thrombosis, has led to the development of a number of parenteral
and oral glycoprotein (GP) IIb/IIIa inhibitors for use in cardiovascular disease states, such as acute coronary syndromes
and stroke. The predominant effect of these agents is to inhibit platelet aggregation, although studies of αIIbβ3 receptor function and various GP IIb/IIIa inhibitors have demonstrated the potential for these agents to produce effects
on other aspects of platelet function, in addition to non-platelet effects. Overall, clinical studies have demonstrated an
impressive beneficial effect for parenteral agents in reducing ischemic complications following percutaneous intervention,
and a more modest beneficial effect in the treatment of patients with acute coronary syndromes. Trials with oral GP IIb/IIIa
inhibitors in similar patient populations have demonstrated toxicity, manifested by an increased mortality in treated patients.
Increased understanding of molecular aspects of both αIIbβ3 receptor function and the effects of GP IIb/IIIa inhibition may help explain some of the inconsistency in recently reported
clinical studies with parenteral agents, and the frank toxicity of oral agents. Such studies may also hold the key to the
development of newer agents with enhanced therapeutic benefit.
Received 10 September 2001; received after revision 22 October 2001; accepted 2 November 2001 相似文献