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1.
Skeie GO 《Cellular and molecular life sciences : CMLS》2000,57(11):1570-1576
Titins are a family of gigantic filamentous muscle proteins essential for muscle structure, function and development. Most of their sequence consists of repetitive modules of two superfamily motifs, immunoglobulin and fibronectin, interspersed with unique sequences. A special feature is that many regions are differentially expressed in different muscle types, providing unique characteristics. Titin is evolutionarily old, and many regions are highly conserved. Most mutations that alter titin's characteristics seem to be incompatible with life, since very few associated genetic diseases have been described. The autoimmune response against titin in the paraneoplastic form of myasthenia gravis is discussed. 相似文献
2.
Sarramegn V Muller I Milon A Talmont F 《Cellular and molecular life sciences : CMLS》2006,63(10):1149-1164
G protein-coupled receptors (GPCRS) represent a class of integral membrane proteins involved in many biological processes
and pathologies. Fifty percent of all modern drugs and almost 25% of the top 200 bestselling drugs are estimated to target
GPCRs. Despite these crucial biological implications, very little is known, at atomic resolution, about the detailed molecular
mechanisms by which these membrane proteins are able to recognize their extra-cellular stimuli and transmit the associated
messages. Obviously, our understanding of GPCR functioning would be greatly facilitated by the availability of high-resolution
three-dimensional (3D) structural data. However, expression, solubilization and purification of these membrane proteins are
not easy to achieve, and at present, only one 3D structure has been determined, that of bovine rhodopsin. This review presents
and compares the different successful strategies which have been applied to solubilize and purify recombinant GPCRs in the
perspective of structural biology experiments.
Received 21 November 2005; received after revision 20 January 2006; accepted 2 February 2006
An erratum to this article is available at . 相似文献
3.
Katja Gehrig-Burger Jirina Slaninova Gerald Gimpl 《Cellular and molecular life sciences : CMLS》2010,67(16):2815-2824
Progesterone non-genomically attenuates the calcium signaling of the human oxytocin receptor and several other Gαq protein-coupled receptors. High progesterone concentrations are found in the endometrium during pregnancy opposing the responsiveness
of the underlying myometrium to labor-inducing hormones. Here, we demonstrate that within minutes, progesterone inhibits oxytocin-
and bradykinin-induced contractions of rat uteri, calcium responses induced by platelet-activating factor in the human endometrial
cell line MFE-280, and oxytocin-induced calcium signals in PHM1-31 immortalized pregnant human myometrial cells. Using human
embryonic kidney (HEK293) cells as model system, we analyzed the molecular mechanisms underlying these effects. Our data indicate
that progesterone rapidly depletes intracellular calcium stores. The resulting desensitization of the cells might contribute
to the quiescence of the uterus during pregnancy. 相似文献
4.
C Bauer 《Experientia》1990,46(11-12):1157-1160
5.
Alternative splicing of Bcl-2-related genes: functional consequences and potential therapeutic applications 总被引:6,自引:0,他引:6
Apoptosis is a morphologically distinct form of cell death. It is executed and regulated by several groups of proteins. Bcl-2 family proteins are the main regulators of the apoptotic process acting either to inhibit or promote it. More than 20 members of the family have been identified so far and most have two or more isoforms. Alternative splicing is one of the major mechanisms providing proteomic complexity and functional diversification of the Bcl-2 family proteins. Pro- and anti-apoptotic Bcl-2 family members should function in harmony for the regulation of the apoptosis machinery, and their relative levels are critical for cell fate. Any mechanism breaking down this harmony by changing the relative levels of these antagonistic proteins could contribute to many diseases, including cancer and neurodegenerative disorders. Recent studies have shown that manipulation of the alternative splicing mechanisms could provide an opportunity to restore the proper balance of these regulator proteins. This review summarises current knowledge on the alternative splicing products of Bcl-2-related genes and modulation of splicing mechanisms as a potential therapeutic approach.Received 5 January 2004; received after revision 31 March 2004; accepted 6 April 2004 相似文献
6.
Patricio Atanes Inmaculada Ruz-Maldonado Ross Hawkes Bo Liu Min Zhao Guo Cai Huang Israa Mohammed Al-Amily Albert Salehi Stefan Amisten Shanta J. Persaud 《Cellular and molecular life sciences : CMLS》2018,75(16):3039-3050
Introduction
Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.Materials and methods
GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC. The pathways connecting GPCR peptide ligands with their receptors were identified by manual searches in the PubMed, IUPHAR and Ingenuity databases. Distribution of PYY protein in mouse and human islets was determined by immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets was measured by radioimmunoassay.Results
We have quantified GPCR peptide ligand mRNA expression in human and mouse islets and created specific signalomes mapping the pathways by which islet peptide ligands regulate human and mouse GPCR signalling. We also identified species-specific islet expression of several GPCR ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than human islets, suggesting a more important role of locally secreted Pyy in mouse islets. This was confirmed by IHC and functional experiments measuring insulin, glucagon and somatostatin secretion.Discussion
The detailed human and mouse islet GPCR peptide ligand atlases will allow accurate translation of mouse islet functional studies for the identification of GPCR/peptide signalling pathways relevant for human physiology, which may lead to novel treatment modalities of diabetes and metabolic disease.7.
The vertebrate olfactory system recognizes and discriminates between thousands of structurally diverse odorants. Detection of odorants in mammals is mediated by olfactory receptors (ORs), which comprise the largest superfamily of G protein-coupled receptors (GPCRs). Upon odorant binding, ORs couple to G proteins, resulting in an increase in intracellular cAMP levels and subsequent receptor signaling. In this review, we will discuss recently published studies outlining the molecular basis of odor discrimination, focusing on pharmacology, G protein activation, and desensitization of ORs. A greater understanding of the molecular mechanisms underlying OR activity may help in the discovery of agonists and antagonists of ORs, and of GPCRs with potential therapeutic applications. 相似文献
8.
Bjarnadóttir TK Fredriksson R Schiöth HB 《Cellular and molecular life sciences : CMLS》2007,64(16):2104-2119
G protein-coupled receptors (GPCRs) are a diverse superfamily of membrane-bound receptors. The second largest subgroup of
GPCRs, the Adhesion GPCRs, has 33 members in humans. Phylogenetic analysis of the entire repertoire of the seven transmembrane- domain (7TM)
regions of GPCRs shows that the Adhesion GPCRs form a distinct family. Adhesion GPCRs are characterised by (1) long N termini with multiple functional domains often found in other proteins such as tyrosine
kinases, integrins and cadherins, (2) highly complex genomic structure with multiple introns and splice variants and (3) a
7TM region that has no clear similarities with 7TM from other GPCRs. Several Adhesion GPCRs are known to have a role in the immune system but it is becoming more evident that many have important roles in the
CNS. We speculate that the overall structural construction of the Adhesion GPCRs allows them to participate in different types of cell guidance.
Received 8 February 2007; received after revision 21 March 2007; accepted 25 April 2007 相似文献
9.
R. F. Vollman 《Cellular and molecular life sciences : CMLS》1959,15(10):407-408
Zusammenfassung Der Bericht schildert die Entwicklung des PhilologiestudentenCarl G. Hartman zum Naturwissenschaftler. Studien über pilzzüchtende Ameisen und über die Ökologie solitärer Wespen folgten embryologische Versuche bei Fledermäusen. Mit hier anschliessenden Untersuchungen zur Fortpflanzungsphysiologie und frühen Embryonalperiode des Opossums und des Rhesusaffen hatHartman einen grundlegenden Beitrag zur modernen Fortpflanzungsphysiologie geleistet.
Paper read at his eightieth birthday, June 3, 1959. 相似文献
Paper read at his eightieth birthday, June 3, 1959. 相似文献
10.
The identification of chemokines in blood platelets has strengthened our view of these cells as participants in immune host
defense. Platelet chemokines representing prestored and rapidly releasable proteins may play a major role as first-line inflammatory
mediators. This is evident from their capability to recruit early inflammatory cells such as neutrophil granulocytes and monocytes
and even to exhibit direct antimicrobial activity. However, insight is growing that platelet chemokines may be also long-term
regulators, e.g., by activating T lymphocytes, by modulating the formation of endothelium and even thrombocytopoiesis itself.
This review deals with the individual and cooperative functionality of platelet chemokines, as well as their potential as
a basis for therapeutic intervention in the pathology of inflammation, infection, allergy and tumors. Within this context,
therapeutic strategies based on the use of antibodies, modified chemokines, chemokine-binding proteins and chemokine receptor
antagonists as well as first clinical studies will be addressed. 相似文献
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Astrid Musnier Domitille Heitzler Thomas Boulo Sophie Tesseraud Guillaume Durand Charlotte Lécureuil Hervé Guillou Anne Poupon Eric Reiter Pascale Crépieux 《Cellular and molecular life sciences : CMLS》2009,66(21):3487-3503
The mechanisms whereby G protein-coupled receptors (GPCR) activate signalling pathways involved in mRNA translation are ill-defined,
in contrast to tyrosine kinase receptors (TKR). We compared a GPCR and a TKR, both endogenously expressed, for their ability
to mediate phosphorylation of 70-kDa ribosomal S6 kinase p70S6K in primary rat Sertoli cells at two developmental stages.
In proliferating cells stimulated with follicle-stimulating hormone (FSH), active p70S6K was phosphorylated on T389 and T421/S424,
through cAMP-dependent kinase (PKA) and phosphatidyl-inositide-3 kinase (PI3K) antagonizing actions. In FSH-stimulated differentiating
cells, active p70S6K was phosphorylated solely on T389, PKA and PI3K independently enhancing its activity. At both developmental
stages, insulin-induced p70S6K regulation was consistent with reported data. Therefore, TKR and GPCR trigger distinct p70S6K
active conformations. p70S6K developmental regulation was formalized in a dynamic mathematical model fitting the data, which
led to experimentally inaccessible predictions on p70S6K phosphorylation rate. 相似文献
13.
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
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M. B. Qumsiyeh 《Cellular and molecular life sciences : CMLS》1999,55(8-9):1129-1140
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Summary and conclusions The recent characterization of the human insulin receptor structure and its intrinsic tyrosine kinase activity represent major advances in our understanding of the mechanism of insulin action. It is reasonable to think that the insulin-induced autophosphorylation and activation of its receptor kinase represent an important event in the action of insulin on cell metabolism and growth. The fundamental research reviewed may be followed by the discovery of molecular receptor defects in clinical syndromes of insulin resistance. 相似文献