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1.
The structure and function of heterotrimeric G protein subunits is known in considerable detail. Upon stimulation of a heptahelical
receptor by the appropriate agonists, the cognate G proteins undergo a cycle of activation and deactivation; the α-subunits and the βγ-dimers interact sequentially with several reaction partners (receptor, guanine nucleotides and effectors as well as regulatory
proteins) by exposing appropriate binding sites. For most of these domains, low molecular weight ligands have been identified
that either activate or inhibit signal transduction. These ligands include short peptides derived from receptors, G protein
subunits and effectors, mastoparan and related insect venoms, modified guanine nucleotides, suramin analogues and amphiphilic
cations. Because compounds that act on G proteins may be endowed with new forms of selectivity, we propose that G protein
subunits may therefore be considered as potential drug targets.
Received 18 September 1998; received after revision 6 November 1998; accepted 11 November 1998 相似文献
2.
δ-Protocadherins constitute a group of cadherins characterized by several conserved motifs in their cytoplasmic domains. We
present a phylogenetic analysis that further divides this group into δ1-protocadherins (comprising protocadherin-1, −7, −9
and −11 or -X/Y) and δ2-protocadherins (comprising protocadherin-8, −10, −17, −18 and −19). The δ-protocadherin genes, which
are located on different chromosomes in man and mouse, have a similar gene structure. They are expressed as multiple splice
forms, differing mostly in their cytoplasmic domains. Some δ-protocadherins were reported to mediate weak cell-cell adhesion
in vitro and cell sorting in vivo. In addition, individual δ-protocadherins might play important roles in signaling pathways,
as they bind to proteins such as TAF1/Set, protein phosphatase-1α and the Frizzled 7 receptor. The spatiotemporally restricted
expression of δ-protocadherins in different tissues and species and the results of their functional analysis, mainly in Xenopus, suggest that they play multiple, tightly regulated roles in vertebrate development.
Received 18 July 2005; received after revision 26 August 2005; accepted 2 September 2005 相似文献
3.
Malaguarnera L 《Cellular and molecular life sciences : CMLS》2006,63(24):3018-3029
The enzyme chitotriosidase (ChT), the human analogue of chitinases from non-vertebrate species, is one of the most abundant
and indicative proteins secreted by activated macrophages. Its enzymatic activity is elevated in serum of patients suffering
from Gaucher’s disease type 1 and in some other inherited lysosomal storage disorders, as well as in diseases in which macrophages
are activated. The last decade has witnessed the appearance of a substantial number of studies attempting to unravel its cellular
functions, which have yet not been fully defined. A great deal of progress has been made in the study of the physiological
roles of ChT. This review is looks at the key areas of investigations addressed to further illuminate whether ChT activation
might have different functional meanings in various diseases.
Received 7 June 2006; received after revision 24 July 2006; accepted 21 September 2006 相似文献
4.
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
5.
6.
Huet J Wyckmans J Wintjens R Boussard P Raussens V Vandenbussche G Ruysschaert JM Azarkan M Looze Y 《Cellular and molecular life sciences : CMLS》2006,63(24):3042-3054
Two chitinases, able to use tetra-N-acetylglucosamine, chitin and chitosan as substrates, were characterized after purification from Carica papaya latex. The complete amino acid sequence of the major form and about 40% of the minor one were determined through proteolytic
digestions and mass spectroscopy analysis. Sequencing demonstrated that both papaya chitinases are members of the family 19
of glycosyl hydrolases (GH19). Based on the known 3-D structures of other members of family GH19, it was expected that papaya
chitinases would adopt all-alpha structures. However, circular dichroism and infrared spectroscopy indicated, for the papaya
chitinases, a content of 15–20% of extended structures besides the expected 40% of alpha helices. Since the fully sequenced
papaya chitinase contains a large number of proline residues the possibility that papaya chitinase contains polyproline II
stretches was examined in the context of their resistance against proteolytic degradation.
Received 11 July 2006; received after revision 13 October 2006; accepted 25 October 2006 相似文献
7.
S. C. van Buul-Offers R. Kooijman 《Cellular and molecular life sciences : CMLS》1998,54(10):1083-1094
Growth hormone (GH) and insulin-like growth factor I (IGF-I) can modulate the development and function of the immune system.
In this chapter, we present data on the expression of receptors for GH and IGFs and the in vitro and in vivo effects of these
proteins. We show that expression of GH and IGFs in the immune system opens up the possibility that these proteins are not
only involved in endocrine control of the immune system but can also play a role as local growth and differentiation factors
(cytokines). Endocrine control of GH could be direct or mediated via endocrine or autocrine/paracrine IGF-I. In addition,
GH can act as an autocrine or paracrine factor itself. Furthermore, IGF-I in the immune system has been shown to be regulated
by cytokines, such as interleukin-1 and interferon-γ, alluding to a cytokine-like function of IGF-I. In addition to data on the function of GH and IGF-I in the immune system,
we present new findings which imply a possible function of IGF-II and IGF-binding proteins. 相似文献
8.
T. Hubert S. Grimal P. Carroll A. Fichard-Carroll 《Cellular and molecular life sciences : CMLS》2009,66(7):1223-1238
Collagens are extracellular proteins characterized by a structure in triple helices. There are 28 collagen types which differ
in size, structure and function. Their architectural and functional roles in connective tissues have been widely assessed.
In the nervous system, collagens are rare in the vicinity of the neuronal soma, occupying mostly a “marginal” position, such
as the meninges, the basement membranes and the sensory end organs. In neural development, however, where various ECM molecules
are known to be determinant, recent studies indicate that collagens are no exception, participating in axonal guidance, synaptogenesis
and Schwann cell differentiation. Insights on collagens function in the brain have also been derived from neural pathophysiological
conditions. This review summarizes the significant advances which underscore the function and importance of collagens in the
nervous system.
Received 09 September 2008; received after revision 24 October 2008; accepted 28 October 2008 相似文献
9.
Ronda Bransteitter Courtney Prochnow Xiaojiang S. Chen 《Cellular and molecular life sciences : CMLS》2009,66(19):3137-3147
The apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family of cytidine deaminases has emerged as an intensively
studied field as a result of their important biological functions. These enzymes are involved in lipid metabolism, antibody
diversification, and the inhibition of retrotransposons, retroviruses, and some DNA viruses. The APOBEC proteins function
in these roles by deaminating single-stranded (ss) DNA or RNA. There are two high-resolution crystal structures available
for the APOBEC family, Apo2 and the C-terminal catalytic domain (CD2) of Apo3G or Apo3G-CD2 [Holden et al. (Nature 456:121–124,
2008); Prochnow et al. (Nature 445:447–451, 2007)]. Additionally, the structure of Apo3G-CD2 has also been determined using
NMR [Chen et al. (Nature 452:116–119, 2008); Furukawa et al. (EMBO J 28:440–451, 2009); Harjes et al. (J Mol Biol, 2009)].
A detailed structural analysis of the APOBEC proteins and a comparison to other zinc-coordinating deaminases can facilitate
our understanding of how APOBEC proteins bind nucleic acids, recognize substrates, and form oligomers. Here, we review the
recent development of structural and functional studies that apply to Apo3G as well as the APOBEC deaminase family. 相似文献
10.
A review of the literature suggests that the effects of nitric oxide (NO) on skeletal muscles fibers can be classified in
two groups. In the first, the effects of NO are direct, due to nitrosation or metal nitrosylation of target proteins: depression
of isometric force, shortening velocity of loaded or unloaded contractions, glycolysis and mitochondrial respiration. The
effect on calcium release channels varies, being inhibitory at low and stimulatory at high NO concentrations. The general
consequence of the direct effects of NO is to ‘brake’ the contraction and its associated metabolism. In the second group,
the effects of NO are mediated by cGMP: increase of the shortening velocity of loaded or unloaded contractions, maximal mechanical
power, initial rate of force development, frequency of tetanic fusion, glucose uptake, glycolysis and mitochondrial respiration;
decreases of half relaxation time of tetanus and twitch, twitch time-to-peak, force maintained during unfused tetanus and
of stimulus-associated calcium release. There is negligible effect on maximal force of isometric twitch and tetanus. The general
consequence of cGMP-mediated effects of NO is to improve mechanical and metabolic muscle power, similar to a transformation
of slow-twitch to fast-twitch muscle, an effect that we may summarize as a ‘slow-to-fast’ shift. 相似文献
11.
M. V. Nogués M. Moussaoui E. Boix M. Vilanova M. Ribó C. M. Cuchillo 《Cellular and molecular life sciences : CMLS》1998,54(8):766-774
The enzymatic catalysis of polymeric substrates such as proteins, polysaccharides or nucleic acids requires precise alignment
between the enzyme and the substrate regions flanking the region occupying the active site. In the case of ribonucleases,
enzyme-substrate binding may be directed by electrostatic interactions between the phosphate groups of the RNA molecule and
basic amino acid residues on the enzyme. Specific interactions between the nitrogenated bases and particular amino acids in
the active site or adjacent positions may also take place. The substrate-binding subsites of ribonuclease A have been characterized
by structural and kinetic studies. In addition to the active site (p1 ), the role of other noncatalytic phosphate-binding subsites in the correct alignment of the polymeric substrate has been
proposed. p2 and p0 have been described as phosphate-binding subsites that bind the phosphate group adjacent to the 3′ side and 5′ side, respectively,
of the phosphate in the active site. In both cases, basic amino acids (Lys-7 and Arg-10 in p2 , and Lys-66 in p0 ) are involved in binding. However, these binding sites play different roles in the catalytic process of ribonuclease A.
The electrostatic interactions in p2 are important both in catalysis and in the endonuclease activity of the enzyme, whilst the p0 electrostatic interaction contributes only to binding of the RNA. 相似文献
12.
13.
A possible new role for the anti-ageing peptide carnosine 总被引:5,自引:0,他引:5
The naturally occurring dipeptide carnosine (β-alanyl-L-histidine) is found in surprisingly large amounts in long-lived tissues and can delay ageing in cultured human fibroblasts.
Carnosine has been regarded largely as an anti-oxidant and free radical scavenger. More recently, an anti-glycating potential
has been discovered whereby carnosine can react with low-molecular-weight compounds that bear carbonyl groups (aldehydes and
ketones). Carbonyl groups, arising mostly from the attack of reactive oxygen species and ow-molecular-weight aldehydes and
ketones, accumulate on proteins during ageing. Here we propose, with supporting evidence, that carnosine can react with protein
carbonyl groups to produce protein-carbonyl-carnosine adducts (‘carnosinylated’ proteins). The various possible cellular fates
of the carnosinylated proteins are discussed. These proposals may help explain anti-ageing actions of carnosine and its presence
in non-mitotic cells of long-lived mammals.
Received 29 November 1999; accepted 27 December 1999 相似文献
14.
Mitchell S. Dushay 《Cellular and molecular life sciences : CMLS》2009,66(16):2643-2650
The clot’s appearance in different large-bodied insects has been described, but until recently, little was known about any
insect clot’s molecular makeup, and few experiments could directly test its function. Techniques have been developed in Drosophila (fruit fly) larvae to identify clotting factors that can then be tested for effects on hemostasis, healing, and immunity.
This has revealed unanticipated complexity in the hemostatic mechanisms in these larvae. While the clot’s molecular structure
is not yet fully understood, progress is being made, and the loss of clotting factors has been shown to cause subtle immune
defects. The few similarities between coagulation in different insect species and life stages, and the current state of knowledge
about coagulation in insects are discussed. 相似文献
15.
Summary The major serum proteins of Dipteran larvae present something of an enigma. In many respects they are extremely well suited for studies on gene structure and control, protein chemistry and physiology. Large amounts of these proteins are synthesized by the fat body at specific stages of larval development, much is known about their biochemistry, genetics and evolution and some information is available about the control of their synthesis. There are however doubts as to their function. This article considers what is known about these proteins in Dipterans and other insect groups and relates this information to their evolution and their possible function. 相似文献
16.
Fabian Fernandez Viviana Torres Pedro Zamorano 《Cellular and molecular life sciences : CMLS》2010,67(11):1751-1754
Presynaptic differentiation takes place over three interrelated acts involving the biogenesis and trafficking of molecular
complexes of active zone material, the “trapping” or stabilization of active zone sites, and the subsequent development of
mature synapses. Although the identities of proteins involved with establishing presynaptic specializations have been increasingly
delineated, the exact functional mechanisms by which the active zone is assembled remain poorly understood. Here, we discuss
a theoretical model for how the trapping stage of presynaptic differentiation might occur in developing neurons. We suggest that subsets of active zone proteins containing
polyglutamine domains undergo concentration-dependent prion-like conversions as they accumulate at the plasma membrane. This
conversion might serve to aggregate the proteins into a singular structure, which is then able to recruit scaffolding agents
necessary for regulated synaptic transmission. A brief informatics analysis in support of this ‘Q’ assembly hypothesis—across
commonly used models of synaptogenesis—is presented. 相似文献
17.
Polyphenolic phytochemicals are ubiquitous in plants, in which they function in various protective roles. A ‘recommended’
human diet contains significant quantities of polyphenolics, as they have long been assumed to be ‘antioxidants’ that scavenge
excessive, damaging, free radicals arising from normal metabolic processes. There is recent evidence that polyphenolics also
have ‘indirect’ antioxidant effects through induction of endogenous protective enzymes. There is also increasing evidence
for many potential benefits through polyphenolic-mediated regulation of cellular processes such as inflammation. Inductive
or signalling effects may occur at concentrations much lower than required for effective radical scavenging. Over the last
2 – 3 years, there have been many exciting new developments in the elucidation of the in vivo mechanisms of the health benefits of polyphenolics. We summarise the current knowledge of the intake, bio-availability and
metabolism of polyphenolics, their antioxidant effects, regulatory effects on signalling pathways, neuro-protective effects
and regulatory effects on energy metabolism and gut health.
Received 14 May 2007; received after revision 27 June 2007; accepted 24 July 2007 相似文献
18.
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
19.
Ji RC 《Cellular and molecular life sciences : CMLS》2012,69(6):897-914
The lymphatic system provides important functions for tissue fluid homeostasis and immune response. Lymphangiogenesis, the
formation of new lymphatics, comprises a series of complex cellular events in vitro or in vivo, e.g., proliferation, differentiation,
and sprouting. Recent evidence has implied that macrophages act as a direct structural contributor to lymphatic endothelial
walls or secret VEGF-C/-D and VEGF-A to initiate lymphangiogenesis in inflamed or tumor tissues. Bone marrow-derived macrophages
are versatile cells that express different functional programs in response to exposure to microenvironmental signals, and
can be identified by specific expression of a number of proteins, F4/80, CD11b, and CD68. Several causative factors, e.g.,
NF-κB, IL-1β, TNF-α, SDF-1, M-CSF, especially TonEBP/VEGF-C signaling, may be actively involved in macrophage-induced lymphangiogenesis.
Alteration of macrophage phenotype and function has a profound effect on the development and progression of inflammation and
malignancy, and macrophage depletion for controlling lymphangiogenesis may provide a novel approach for prevention and treatment
of lymphatic-associated diseases. 相似文献
20.
Laitinen OH Hytönen VP Nordlund HR Kulomaa MS 《Cellular and molecular life sciences : CMLS》2006,63(24):2992-3017
Chicken avidin and bacterial streptavidin, (strept)avidin, are proteins widely utilized in a number of applications in life
science, ranging from purification and labeling techniques to diagnostics, and from targeted drug delivery to nanotechnology.
(Strept)avidin-biotin technology relies on the extremely tight and specific affinity between (strept)avidin and biotin (dissociation
constant, Kd≈10−14–10−16 M). (Strept)avidins are also exceptionally stable proteins. To study their ligand binding and stability characteristics,
the two proteins have been extensively modified both chemically and genetically. There are excellent accounts of this technology
and chemically modified (strept)avidins, but no comprehensive reviews exist concerning genetically engineered (strept)avidins.
To fill this gap, we here go through the genetically engineered (strept)avidins, summarizing how these constructs were designed
and how they have improved our understanding of the structural and functional characteristics of these proteins, and the benefits
they have provided for (strept)avidin-biotin technology.
Received 22 June 2006; received after revision 1 August 2006; accepted 21 September 2006 相似文献