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1.
Sardha P. Suriyapperuma Larissa Lozovatsky Steven L. Ciciotte Luanne L. Peters Diana M. Gilligan 《Mammalian genome》2000,11(1):16-23
Mouse cDNA sequences encoding α, β, and γ adducins were cloned from a mouse reticulocyte cDNA library. The purified clones
contain alternatively spliced exons from all three adducin genes. In the case of α and β, the inclusion of the alternatively
spliced exons results in truncated polypeptide isoforms (called α-2 and β-2). The mouse predicted amino acid sequences are
compared with published rat and human sequences. For completion of this comparison, cDNA encoding the rat β-1 carboxy terminus
was cloned by PCR. The carboxy terminal region containing MARCKS homology, calmodulin-binding region-2, and spectrin-actin-binding
site, is conserved among α-1, β-1, and γ-1 isoforms in mouse, rat, and humans. We also report here the localization of the
gene encoding γ adducin (Add3) to murine Chr 19, in a region that shows conserved synteny with human Chr 10.
Received: 1 June 1999 / Accepted: 25 August 1999 相似文献
2.
Evolution of the Integrin α and β Protein Families 总被引:4,自引:0,他引:4
Hughes AL 《Journal of molecular evolution》2001,52(1):63-72
A phylogenetic analysis of vertebrate and invertebrate α integrins supported the hypothesis that two major families of vertebrate
α integrins originated prior to the divergence of deuterostomes and protostomes. These two families include, respectively,
the αPS1 and αPS2 integrins of Drosophila melanogaster, and each family has duplicated repeatedly in vertebrates but not in Drosophila. In contrast, a third family (including αPS3) has duplicated in Drosophila but is absent from vertebrates. Vertebrate αPS1 and αPS2 family members are found on human chromosomes 2, 12, and 17. Linkage
of these family members may have been conserved since prior to the origin of vertebrates, and the two genes duplicated simultaneously.
A phylogenetic analysis of β integrins did not clearly resolve whether vertebrate β integrin genes duplicated prior to the
origin of vertebrates, although it suggested that at least the gene encoding vertebrate β4 may have done so. In general, the
phylogeny of neither α nor β integrins showed a close correspondence with patterns of α–β heterodimer formation or other functional
characteristics. One major exception to this trend involved αL, αM, αX, and αD, a monophyletic group of immune cell-expressed
α integrins, which share a number of common functional characteristics and have evolved in coordinated fashion with their
β integrin partners.
Received: 22 June 2000 / Accepted: 11 September 2000 相似文献
3.
Clustered protocadherin family 总被引:1,自引:0,他引:1
Takeshi Yagi 《Development, growth & differentiation》2008,50(S1):S131-S140
The brain is a complex system composed of enormous numbers of differentiated neurons, and brain structure and function differs among vertebrates. To examine the molecular mechanisms underlying brain structure and function, it is important to identify the molecules involved in generating neural diversity and organization. The clustered protocadherin (Pcdh) family is the largest subgroup of the diverse cadherin superfamily. The clustered Pcdh proteins are predominantly expressed in the brain and their gene structures in vertebrates are diversified. In mammals, the clustered Pcdh family consists of three gene clusters: Pcdh -α, Pcdh -β, and Pcdh -γ. During brain development, this family is upregulated by neuronal differentiation, and Pcdh-α is then dramatically downregulated by myelination. Clustered Pcdh expression continues in the olfactory bulb, hippocampus, and cerebellum until adulthood. Structural analysis of the first cadherin domain of the Pcdh-α protein revealed it lacks the features that classical cadherins require for homophilic adhesiveness, but it contains Pcdh-specific loop structures. In Pcdh-α, an RGD motif on a specific loop structure binds β1-integrin. For gene expression, the gene clusters are regulated by multiple promoters and alternative cis splicing. At the single-cell level, several dozen Pcdh -α and -γ mRNA are regulated monoallelically, resulting in the combinatorial expression of distinct variable exons. The Pcdh-α and Pcdh-γ proteins also form oligomers, further increasing the molecular diversity at the cell surface. Thus, the unique features of the clustered Pcdh family may provide the molecular basis for generating individual cellular diversity and the complex neural circuitry of the brain. 相似文献
4.
5.
GABAA receptors composed of α, β and γ subunits display a significantly higher single-channel conductance than receptors comprised
of only α and β subunits. The pore of GABAA receptors is lined by the second transmembrane region from each of its five subunits and includes conserved threonines at
the 6′, 10′ and 13′ positions. At the 2′ position, however, a polar residue is present in the γ subunit but not the α or β
subunits. As residues at the 2′, 6′ and 10′ positions are exposed in the open channel and as such polar channel-lining residues
may interact with permeant ions by substituting for water interactions, we compared both the single-channel conductance and
the kinetic properties of wild-type α1β1 and α1β1γ2S receptors with two mutant receptors, αβγ(S2′A) and αβγ(S2′V). We found
that the single-channel conductance of both mutant αβγ receptors was significantly decreased with respect to wild-type αβγ,
with the presence of the larger valine side chain having the greatest effect. However, the conductance of the mutant αβγ receptors
remained larger than wild-type αβ channels. This reduction in the conductance of mutant αβγ receptors was observed at depolarized
potentials only (ECl = −1.8 mV), which revealed an asymmetry in the ion conduction pathway mediated by the γ2′ residue. The substitutions at the
γ2′ serine residue also altered the gating properties of the channel in addition to the effects on the conductance with the
open probability of the mutant channels being decreased while the mean open time increased. The data presented in this study
show that residues at the 2′ position in M2 of the γ subunit affects both single-channel conductance and receptor kinetics. 相似文献
6.
Beauséjour M Noël D Thibodeau S Bouchard V Harnois C Beaulieu JF Demers MJ Vachon PH 《Apoptosis : an international journal on programmed cell death》2012,17(6):566-578
In human intestinal epithelial crypt (HIEC) cells, the PI3-K/Akt-1 pathway is crucial for the promotion of cell survival and
suppression of anoikis. Class I PI3-K consists of a complex formed by a catalytic (C) and regulatory (R) subunit. Three R
(p85α, β, and p55γ) and four C (p110α, β, γ and δ) isoforms are known. Herein, we analyzed the expression of PI3-K isoforms
in HIEC cells and determined their roles in cell survival, as well as in the β1 integrin/Fak/Src-mediated suppression of anoikis.
We report that: (1) the predominant PI3-K complexes expressed by HIEC cells are p110α/p85β and p110α/p55γ; (2) the inhibition
and/or siRNA-mediated expression silencing of p110α, but not that of p110β, γ or δ, results in Akt-1 down-activation and consequent
apoptosis; (3) the expression silencing of p85β or p55γ, but not that of p85α, likewise induces Akt-1 down-activation and
apoptosis; however, the impact of a loss of p55γ on both Akt-1 activation and cell survival is significantly greater than
that from the loss of p85β; and (4) both the p110α/p85β and p110α/p55γ complexes are engaged by β1 integrin/Fak/Src signaling;
however, the engagement of p110α/p85β is primarily Src-dependent, whereas that of p110α/p55γ is primarily Fak-dependent (but
Src-independent). Hence, HIEC cells selectively express PI3-K isoform complexes, translating into distinct roles in Akt-1
activation and cell survival, as well as in a selective engagement by Fak and/or Src within the context of β1 integrin/Fak/Src-mediated
suppression of anoikis. 相似文献
7.
A carbohydrate-binding module from family 13 (CBM13), appended to the catalytic domain of endo-1,3-β-glucanase from Cellulosimicrobium cellulans, was overexpressed in E. coli, and its interactions with β-glucans, laminarin and laminarioligosaccharides, were analyzed using surface plasmon resonance
biosensor and isothermal titration calorimetry. The association constants for laminarin and laminarioligosaccharides were
determined to be approximately 106 M−1 and 104 M−1, respectively, indicating that 2 or 3 binding sites in the α-, β-, and γ-repeats of CBM13 are involved in laminarin binding
in a cooperative manner. The binding avidity is approximately 2-orders higher than the monovalent binding affinity. Mutational
analysis of the conserved Asp residues in the respective repeats showed that the α-repeat primarily contributes to β-glucan
binding. A Trp residue is predicted to be exposed to the solvent only in the α-repeat and would contribute to β-glucan binding.
The α-repeat bound β-glucan with an affinity of approximately 104 M−1, and the other repeats additionally bound laminarin, resulting in the increased binding avidity. This binding is unique compared
to the recognition mode of another CBM13 from Streptomyces lividans xylanase. 相似文献
8.
Summary Signal transduction across biological membranes is modulated by a family of related GTP-binding proteins termed G proteins.
These G proteins have a heterotrimeric structure composed of α, β, and γ subunits. The α subunits of the G proteins bind GTP
and appear to determine the biochemical specificity of the protein. We have recently cloned and characterized cDNA encoding
two G-protein α subunits, αi and αh. The former is a substrate for ADP-ribosylation by pertussis toxin. The protein corresponding to αh has not yet been identified. These cDNAs encode proteins, which demonstrate 90% sequence identity to one another and also
show marked similarity to other G proteins. The present studies were designed to determine whether the genes for these related
proteins are clustered on a single human chromosome. Genomic DNA isolated from a panel of mouse-human hybrid cell lines was
analyzed by hybridization to cDNAs for αi and αh. Based on the distribution patterns of αi and αh in cell hybrids, the gene for αi was assigned to human chromosome 7, and the gene for αh assigned to chromosome 12. These data suggest that the G-protein gene family may be distributed over at least two human chromosomes. 相似文献
9.
Katarzyna Grzelkowska-Kowalczyk Wioletta Wieteska-Skrzeczyńska 《Cellular & molecular biology letters》2010,15(1):13-31
The aim of this study was to compare the effects of TNF-α, IL-1β and IFN-γ on the activation of protein kinase B (PKB), p70S6k, mitogen-activated protein kinase (MAPK) and p90
rsk
, and on IGF-I-stimulated glucose uptake and protein synthesis in mouse C2C12 myotubes. 100 nmol/l IGF-I stimulated glucose
uptake in C2C12 myotubes by 198.1% and 10 ng/ml TNF-α abolished this effect. Glucose uptake in cells differentiated in the
presence of 10 ng/ml IFN-γ increased by 167.2% but did not undergo significant further modification upon the addition of IGF-I.
IGF-I increased the rate of protein synthesis by 249.8%. Neither TNF-α nor IFN-γ influenced basal protein synthesis, but both
cytokines prevented the IGF-I effect. 10 ng/ml IL-1β did not modify either the basal or IGF-I-dependent glucose uptake and
protein synthesis. With the exception of TNF-α causing an 18% decrease in the level of PKB protein, the cellular levels of
PKB, p70S6k, p42MAPK, p44MAPK and p90
rsk
were not affected by the cytokines. IGF-I caused the phosphorylation of PKB (an approximate 8-fold increase above the basal
value after 40 min of IGF-I treatment), p42MAPK (a 2.81-fold increase after 50 min), and the activation of p70S6k and p90
rsk
, manifesting as gel mobility retardation. In cells differentiated in the presence of TNF-α or IFN-γ, this IGF-I-mediated
PKB and p70S6k phosphorylation was significantly diminished, and the increase in p42MAPK and p90
rsk
phosphorylation was prevented. The basal p42MAPK phosphorylation in C2C12 cells treated with IFN-γ was high and comparable with the activation of this kinase by IGF-I. Pretreatment
of myogenic cells with IL-1β did not modify the IGF-I-stimulated phosphorylation of PKB, p70S6k, p42MAPK and p90
rsk
. In conclusion: i) TNF-α and IFN-γ, but not IL-1β, if present in the extracellular environment during C2C12 myoblast differentiation,
prevent the stimulatory action of IGF-I on protein synthesis. ii) TNF-α- and IFN-γ-induced IGF-I resistance of protein synthesis
could be associated with the decreased phosphorylation of PKB and p70S6k. iii) The activation of glucose uptake in C2C12 myogenic cells treated with IFN-γ is PKB independent. iv) The similar effects
of TNF-α and IFN-γ on the signalling and action of IGF-I on protein synthesis in myogenic cells could suggest the involvement
of both of these cytokines in protein loss in skeletal muscle. 相似文献
10.
11.
H. J. Carlisle T. G. Hales B. A. Schlinger 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1998,182(4):531-538
Songbirds are widely studied to investigate the hormonal control of behavior. However, little is known about the effects
of steroids on neurotransmission in these birds. We used electrophysiological and pharmacological techniques to characterize
γ-aminobutyric acid (GABA) type A receptors (GABAA) of primary cultured telencephalic and hippocampal neurons from developing zebra finches. Additionally, their modulation
by 17β-estradiol(E2), 5α- and 5β-dihydrotestosterone (DHT), 5α- and 5β-pregnan-3α-ol-20-one, and corticosterone was examined. Whole-cell GABA-evoked
currents were inhibited by picrotoxin (10 μmol l−1) and bicuculline methiodide (10 μmol l−1) and potentiated by pentobarbital (100 μmol l−1) and propofol (3 μmol l−1). Loreclezole (10 μmol l−1) potentiated GABA-evoked currents, suggesting the presence of β2, β3 and/or β4 subunits. Diazepam (1 μmol l−1) potentiated currents, while Zn2+ (1 μmol l−1) caused no inhibition, indicating the presence of γ subunits. 5α- and 5β-Pregnan-3α-ol-20-one (100 nmol l−1) potentiated currents, whereas E2 (1 μmol l−1), 5α- and 5β-DHT (1 μmol l−1), and corticosterone (10 μmol l−1) had no detectable effect. We conclude that zebra finch telencephalic and hippocampal GABAA receptors include α, β, and γ subunits and are similar to their mammalian counterparts in both their biophysical and pharmacological
properties. Additionally, GABA-evoked currents are greatly potentiated by 5α- and 5β-pregnan-3α-ol-20-one but show little
or no acute modulation by sex steroids or corticosterone.
Accepted: 12 November 1997 相似文献
12.
The mechanism of lead (Pb2+)-induced neurotoxicity has not yet been fully elucidated. The purpose of this study was to examine the effects of Pb2+ on several protein kinase C (PKC) isoforms and the nuclear factor-κB (NF-κB)–I-κB kinase-alpha (IKK-α) axis in cultured neuronal
cells. Neurons were isolated from rat fetal brain at the 18th day of gestation of pregnant Sprague Dawley rats and cultured
for 10 days before use. Neurons were exposed to Pb2+ at concentrations of 10−10, 10−9, 10−8, and 10−7 mol/L for 14 h and antigens of typical PKC-α,β,γ; novel PKC (ε, δ), atypical PKC (λ), NF-κB (p50), and IKK-α were enriched
by immunoprecipitation and determined by western blotting. Total, calcium-dependent and independent PKC activities were also
determined by counting the transferred γ-32 P in the substrate-histone. The results indicated that inorganic Pb2+ significantly reduced all PKC isoforms (α,β,γ, ε, λ) except δ, inhibiting the total, calcium-dependent and calcium-independent
PKC activities in a dose-dependent manner. Additionally, Pb2+ gradually reduced NF-κB (p50) and IKK-α protein levels. This suggests that Pb2+ exhibits varying preference for individual PKC isoforms but reduces the NF-κB–IKK-α axis to a similar extent. 相似文献
13.
14.
The sequence specific 1H, 13C, and 15N resonance assignments of Hahellin, a putative member of βγ-crystallin family, from Hahella Chejuensis, have been accomplished by NMR spectroscopy. The resonance assignments reveal that the protein adopts predominantly a β-sheet
conformation as in the case of βγ-crystallin folds. 相似文献
15.
Recent studies have revealed an unexpected synergism between two seemingly unrelated protein families: CCN matricellular proteins
and the tumor necrosis factor (TNF) family of cytokines. CCN proteins are dynamically expressed at sites of injury repair
and inflammation, where TNF cytokines are also expressed. Although TNFα is an apoptotic inducer in some cancer cells, it activates
NFκB to promote survival and proliferation in normal cells, and its cytotoxicity requires inhibition of de novo protein synthesis
or NFκB signaling. The presence of CCN1, CCN2, or CCN3 overrides this requirement and unmasks the apoptotic potential of TNFα,
thus converting TNFα from a proliferation-promoting protein into an apoptotic inducer. These CCN proteins also enhance the
cytotoxicity of other TNF cytokines, including LTα, FasL, and TRAIL. Mechanistically, CCNs function through integrin α6β1 and the heparan sulfate proteoglycan (HSPG) syndecan-4 to induce reactive oxygen species (ROS) accumulation, which is essential
for apoptotic synergism. Mutant CCN1 proteins defective for binding α6β1-HSPGs are unable to induce ROS or apoptotic synergism with TNF cytokines. Further, knockin mice that express an α6β1-HSPG-binding defective CCN1 are blunted in TNFα- and Fas-mediated apoptosis, indicating that CCN1 is a physiologic regulator
of these processes. These findings implicate CCN proteins as contextual regulators of the inflammatory response by dictating
or enhancing the cytotoxicity of TNFα and related cytokines. 相似文献
16.
Evolutionary Relationship of the Ligand-Gated Ion Channels and the Avermectin-Sensitive,Glutamate-Gated Chloride Channels 总被引:4,自引:0,他引:4
Demetrios K. Vassilatis Keith O. Elliston Philip S. Paress Michel Hamelin Joseph P. Arena James M. Schaeffer Lex H.T. Van der Ploeg Doris F. Cully 《Journal of molecular evolution》1997,44(5):501-508
Two cDNAs, GluClα and GluClβ, encoding glutamate-gated chloride channel subunits that represent targets of the avermectin
class of antiparasitic compounds, have recently been cloned from Caenorhabditis elegans (Cully et al., Nature, 371, 707–711, 1994). Expression studies in Xenopus oocytes showed that GluClα and GluClβ have pharmacological profiles distinct from the glutamate-gated cation channels as
well as the γ-aminobutyric acid (GABA)- and glycine-gated chloride channels. Establishing the evolutionary relationship of
related proteins can clarify properties and lead to predictions about their structure and function. We have cloned and determined
the nucleotide sequence of the GluClα and GluClβ genes. In an attempt to understand the evolutionary relationship of these
channels with the members of the ligand-gated ion channel superfamily, we have performed gene structure comparisons and phylogenetic
analyses of their nucleotide and predicted amino acid sequences. Gene structure comparisons reveal the presence of several
intron positions that are not found in the ligand-gated ion channel superfamily, outlining their distinct evolutionary position.
Phylogenetic analyses indicate that GluClα and GluClβ form a monophyletic subbranch in the ligand-gated ion channel superfamily
and are related to vertebrate glycine channels/receptors. Glutamate-gated chloride channels, with electrophysiological properties
similar to GluClα and GluClβ, have been described in insects and crustaceans, suggesting that the glutamate-gated chloride
channel family may be conserved in other invertebrate species. The gene structure and phylogenetic analyses in combination
with the distinct pharmacological properties demonstrate that GluClα and GluClβ belong to a discrete ligand-gated ion channel
family that may represent genes orthologous to the vertebrate glycine channels.
Received: 30 September 1996 / Accepted: 15 November 1996 相似文献
17.
PA28 subunits of the mouse proteasome: primary structures and chromosomal localization of the genes 总被引:2,自引:0,他引:2
The 20S proteasome is a multi-subunit protease responsible for the production of peptides presented by major histocompatibility
complex (MHC) class I molecules. Recent evidence indicates that an interferon-γ (IFN-γ)-inducible PA28 activator complex enhances
the generation of class I binding peptides by altering the cleavage pattern of the proteasome. In the present study, we determined
the primary structures of the mouse PA28 α- and β-subunits. The deduced amino acid sequences of the α- and β-subunits were
49% identical. We also determined the primary structure of the mouse PA28 γ-subunit (Ki antigen), a protein of unknown function
structurally related to the α- and β-subunits. The amino acid sequence identity of the γ-subunit to the α- and β-subunits
was 40% and 32%, respectively. Interspecific backcross mapping showed that the mouse genes coding for the α- and β-subunits
(designated Psme1 and Psme2, respectively) are tightly linked and map close to the Atp5g1 locus on chromosome 14. Thus, unlike the LMP2 and LMP7 subunits, the IFN-γ-inducible subunits of PA28 are encoded outside
the MHC. The gene coding for the γ-subunit (designated Psme3) was mapped to the vicinity of the Brca1 locus on chromosome 11. A computer search of the DNA databases identified a γ-subunit-like protein in ticks and Caenorhabditis elegans, the organisms with no adaptive immune system. It appears that the IFN-γ-inducible α- and β-subunits emerged by gene duplication
from a γ-subunit-like precursor.
Received: 11 March 1997 相似文献
18.
Hexachlorocyclohexane (HCH) has been banned for use in technologically advanced countries; however, it is still in use in
tropical countries like India. Earlier we reported the degradation of HCH isomers by Sphingomonas paucimobilis within 12 days of incubation. Here we report the role of different factors that could enhance the degradation rate of HCH
isomers. We found that an increase in the cell number from 102 to 108 cells/ml resulted in an increased degradation rate of HCH isomers viz. α, β, γ, and δ-HCH. While α-HCH and γ-HCH disappeared
completely from the medium within 3 days of incubation, a maximum of only 90% and 85% degradation was observed for β and δ-HCH,
respectively. We have also observed that adapted cultures degraded HCH isomers more efficiently than did the normal cultures.
Received: 16 February 2000 / Accepted: 23 May 2000 相似文献
19.
20.
Tumor necrosis factor alpha (TNFα) activates the nuclear factor-kappaB (NF-κB) pathway in various cell types, leading to expression
of cell survival and inflammatory proteins. One mechanism of cell survival brought about by NF-κB is the inhibition of Activator
Protein-1 (AP-1), which when activated, could lead to cell death. However, TNFα can also induce the AP-1 pathway, and the
mechanisms by which these two pathways are regulated in response to TNFα are poorly understood. We proposed that Inhibitor
of κB Kinase gamma (IKKγ) (which is also known as NF-κB essential modulator, NEMO) plays a key role in integrating and coordinating
these two pathways. Our results showed that IKKγ activates the AP-1 pathway, via a mechanism that is dependent on the first
leucine zipper (LZ) domain of IKKγ, by interacting with two proteins of the AP-1 complex, c-Jun and c-Fos, and changing the
phosphorylation status of c-Jun. Even though IKKγ is required for the activation of NF-κB, we found that it reduced the activity
of NF-κB when it was overexpressed. In summary, we demonstrated that transfected IKKγ, while inhibiting the NF-κB pathway,
directly interacts with the AP-1 proteins and activates the AP-1 pathway independent of its effects on NF-κB. Our results
indicate that IKKγ regulates TNFα signaling by coordinating cell responses mediated by the AP-1 and NF-κB pathways.
A. S. Shifera and J. M. Friedman contributed equally to this article.
Marshall S. Horwitz—Deceased: This article is dedicated to his loving memory. 相似文献