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81.
Chen SC Kochan JP Campfield LA Burn P Smeyne RJ 《Journal of receptor and signal transduction research》1999,19(1-4):245-266
A high affinity receptor for OB protein was recently cloned from the choroid plexus of mice. At least six alternatively spliced forms of the OB receptor (OB-R) gene have been described, all of which encode proteins containing the OB-R extracellular domain. One splice variant encodes a receptor with a long intracellular domain, OB-RL, that has been implicated in OB-R signaling. Here, we have used in situ hybridization to examine the localization of OB-R splice variants in brain and peripheral tissues of adult and newborn mice. Using a probe hybridizing with all known splice variants, we confirmed that OB-R mRNA was widely distributed in the adult tissues. In the CNS, choroid plexus was the major site of expression. We now demonstrate that OB-R mRNA is expressed in peripheral tissues; primarily associated with connective tissues. In addition, OB-R mRNA was detected at higher levels in peripheral tissues of newborn mice than in adult mice. With a probe specific for OB-RL, we confirmed that high mRNA expression was detected in hypothalamic nuclei, while low levels were observed in choroid plexus. We now report that in peripheral tissues of adult mice, OB-RL mRNA expression was either very low or undetectable. In newborn mice, the pattern of OB-RL message expression in the CNS was similar to that of adult mice, while bone was the site of highest OB-RL message expression in the peripheral tissue. These data suggest different biological roles for OB-R splice variants encoding the short and long forms of OB-R. The localization of OB-RL to hypothalamic nuclei supports the idea that OB-RL is the brain receptor that mediates OB protein signaling and actions. In addition, the expression of OB-R message in newborn mice also suggests a biological role of OB-R during development in mice. 相似文献
82.
Acyl-CoA:monoacylglycerol acyltransferase (MGAT) plays an important role in dietary fat absorption by catalyzing a rate-limiting step in the re-synthesis of diacylglycerols in enterocytes. The present study reports further characterization of MGAT2, a newly identified intestinal MGAT (Cao, J., Lockwood, J., Burn, P., and Shi, Y. (2003) J. Biol. Chem. 278, 13860-13866) for its substrate specificity, requirement for lipid cofactors, optimum pH and Mg2+, and other intrinsic properties. MGAT2 enzyme expressed in COS-7 cells displayed a broad range of substrate specificity toward fatty acyl-CoA derivatives and monoacylglycerols, among which the highest activities were observed with oleoyl-CoA and rac-1-monolauroylglycerol, respectively. MGAT2 appeared to acylate monoacylglycerols containing unsaturated fatty acyls in preference to saturated ones. Lipid cofactors that play roles in signal transduction were shown to modulate MGAT2 activities. In contrast to oleic acid and sphingosine that exhibited inhibitory effects, phosphatidylcholine, phosphatidylserine, and phosphatidic acid stimulated MGAT2 activities. Using recombinant murine MGAT2 expressed in Escherichia coli, we demonstrated conclusively that MGAT2 also possessed an intrinsic acyl-CoA:diacylglycerol acyltransferase (DGAT) activity, which could provide an alternative pathway for triacylglycerol synthesis in the absence of DGAT. In contrast to the inhibitory effect on MGAT2 activities, nonionic and zwitterionic detergents led to a striking activation of DGAT activity of the human DGAT1 expressed in mammalian cells, which further distinguished the behaviors of the two enzymes. The elucidation of properties of MGAT2 will facilitate future development of compounds that inhibit dietary fat absorption as a means to treat obesity. 相似文献
83.
84.
The murid rodent subfamily Sigmodontinae contains 79 genera which are
distributed throughout the New World. The time of arrival of the first
sigmodontines in South America and the estimated divergence time(s) of the
different lineages of South American sigmodontines have been controversial
due to the lack of a good fossil record and the immense number of extant
species. The "early-arrival hypothesis" states that the sigmodontines must
have arrived in South America no later than the early Miocene, at least 20
MYA, in order to account for their vast present-day diversity, whereas the
"late-arrival hypothesis" includes the sigmodontines as part of the
Plio-Pleistocene Great American Interchange, which occurred approximately
3.5 MYA. The phylogenetic relationships among 33 of these genera were
reconstructed using mitochondrial DNA (mtDNA) sequence data from the ND3,
ND4L, arginine tRNA, and ND4 genes, which we show to be evolving at the
same rate. A molecular clock was calibrated for these genes using published
fossil dates, and the genetic distances were estimated from the DNA
sequences in this study. The molecular clock was used to estimate the dates
of the South American sigmodontine origin and the main sigmodontine
radiation in order to evaluate the "early-" and "late-arrival" scenarios.
We estimate the time of the sigmodontine invasion of South America as
between approximately 5 and 9 MYA, supporting neither of the scenarios but
suggesting two possible models in which the invading lineage was either (1)
ancestral to the oryzomyines, akodonts, and phyllotines or (2) ancestral to
the akodonts and phyllotines and accompanied by the oryzomyines. The
sigmodontine invasion of South America provides an example of the advantage
afforded to a lineage by the fortuitous invasion of a previously
unexploited habitat, in this case an entire continent.
相似文献
85.
Previously, treatment of Tamm-Horsfall glycoprotein (THp) from different
donors with endo-beta-galactosidase has been shown to liberate a tetra- and
a Sd(a)-active pentasaccharide, concluding the presence of N-linked
carbohydrate chains containing additional N - acetyllactosamine units.
These type of oligosaccharides were not found in a detailed structure
elucidation of the carbohydrate moiety of THp of one male donor, suggesting
a donor-specific feature for these type of structures. Therefore, THp was
isolated from four healthy male donors and each subjected to
endo-beta-galactosidase treatment in order to release these tetra- and
Sd(a)-active pentasaccharide. Differences were observed in the total amount
of released tetra- and Sda-active pentasaccharide of the used donors (42,
470, 478, 718 microg/100 mg THp), indicating that the presence of repeating
N-acetyllactosamine units incorporated into the N-glycan moiety of THp is
donor specific. Furthermore, a higher expression of the Sd(a) determinant
on antennae which display N-acetyllactosamine elongation was observed,
suggesting a better accessibility for the
beta-N-acetylgalactosaminyltransferase. In order to characterize the
N-glycans containing repeating N- acetyllactosamine units, carbohydrate
chains were enzymatically released from THp and isolated. The
tetraantennary fraction, which accounts for more than 33% of the total
carbohydrate moiety of THp, was used to isolate oligosaccharides containing
additional N - acetyllactosamine units. Five N-linked tetraantennary
oligosaccharides containing a repeating N-acetyllactosamine unit were
identified, varying from structures bearing four Sd(a) determinants to
structures containing no Sd(a) determinant (see below). One compound was
used in order to specify the branch location of the additional N-
acetyllactosamine unit, and it appeared that only the Gal-6' and Gal-8'
residues were occupied by a repeating N -acetyllactosamine unit.
相似文献
86.
Activation of p56lck by p72syk through physical association and N-terminal tyrosine phosphorylation. 总被引:7,自引:1,他引:6
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C Couture G Baier C Oetken S Williams D Telford A Marie-Cardine G Baier-Bitterlich S Fischer P Burn A Altman et al. 《Molecular and cellular biology》1994,14(8):5249-5258
The p56lck and p59fyn protein tyrosine kinases are important signal transmission elements in the activation of mature T lymphocytes by ligands to the T-cell antigen receptor (TCR)/CD3 complex. The lack of either kinase results in deficient early signaling events, and pharmacological agents that block tyrosine phosphorylation prevent T-cell activation altogether. After triggering of the TCR/CD3 complex, both kinases are moderately activated and begin to phosphorylate cellular substrates, but the molecular mechanisms responsible for these changes have remained unclear. We recently found that the p72syk protein tyrosine kinase is physically associated with the TCR/CD3 complex and is rapidly tyrosine phosphorylated and activated by receptor triggering also in T cells lacking p56lck. Here we examine the regulation of p72syk and its interaction with p56lck in transfected COS-1 cells. p72syk was catalytically active and heavily phosphorylated on its putative autophosphorylation site, Tyr-518/519. Mutation of these residues to phenylalanines abolished its activity in vitro and toward cellular substrates in vivo and reduced its tyrosine phosphorylation in intact cells by approximately 90%. Coexpression of lck did not alter the catalytic activity of p72syk, but the expressed p56lck was much more active in the presence of p72syk than when expressed alone. This activation was also seen as increased phosphorylation of cellular proteins. Concomitantly, p56lck was phosphorylated at Tyr-192 in its SH2 domain, and a Phe-192 mutant p56lck was no longer phosphorylated by p72syk. Phosphate was also detected in p56lck at Tyr-192 in lymphoid cells. These findings suggest that p56lck is positively regulated by the p72syk kinase. 相似文献
87.
Wingfield BD; Grant WS; Wolfaardt JF; Wingfield MJ 《Molecular biology and evolution》1994,11(3):376-383
The genus Ceratocystis sensu stricto includes important fungal pathogens of
woody and herbaceous plants. This genus is distinguished from species in
Ceratocystis sensu lato by the presence of Chalara anamorphs. Ascospore
shape has been used extensively in delineating Ceratocystis taxa, which
show a large variety of ascospore shapes. Sequence analysis of one region
of he 18S ribosomal RNA subunit and two regions of the 28S ribosomal RNA
subunit showed that there was a majority of multiple substitutions at
nucleotide sites and that there was a low transition/transversion ratio, T
= 0.72. Both of these results suggest that these are well established, old
species. Ascospore morphology, for the most part, was not congruent with
the molecular phylogeny, and the use of morphological characters may be
misleading in the taxonomy of these species.
相似文献
88.
Membrane compartmentalized ATP and its preferential use by the Na, K-ATPase of human red cell ghosts
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This paper describes work which begins to define the molecular organization in the region of the membrane that comprises the functional domain of the Na:K pump. The membrane-bound phosphoglycerate kinase (PGK) and Na, K-ATPase appear to be directly linked via a compartmentalized form of ATP. Evidence for the membrane pool of ATP is based on the labeling characteristics of the phosphoproteins by [γ-(32)P]ATP of ghosts incubated under various conditions. Preincubation of ghosts in the presence of ATP at 37 degrees C, but not at 0 degrees C, completely obscures the formation of the Na-phosphoprotein in ghosts washed and subsequently incubated in the presence of [gamma-(32)P]ATP. In contrast to the Na component, the Mg component of phosphorylation is only slightly altered by preincubation with ATP. ATPase activity measured as (32)P(i) liberated during the subsequent incubation at 0 degrees C, reflects completely the differential effects of preincubation with ATP on (32)P incorporation into phosphoprotein. ATP placed within the pool by preincubation can be removed by operating the Na, K-ATPase or the PGK reaction in the reverse direction by use of exogenous substrates. Alternatively, the membrane pool of ATP can be formed also from exogenous substrates by running the PGK reaction in the forward direction. These results, while providing direct support for a membrane compartment of ATP, also indicate the location of this compartment in relation to the PGK and the Na, K-ATPase. In addition, these results also imply that the Mg and Na components are different enzymatic entities since substrate ATP can be derived from separate sources. 相似文献
89.
90.
Georg Zenner Thomas Vorherr Tomas Mustelin Paul Burn 《Journal of cellular biochemistry》1996,63(1):94-103
A biotin-streptavidin-based technique was developed for high affinity, unidirectional, and specific immobilization of synthetic peptides to a solid phase. Biotinylated 23-mer carboxamide peptides corresponding to the three immunoreceptor tyrosine-based activation motifs (ITAMs) of the T cell antigen receptor associated ζ-chain (TCR-ζ) in their bis-, mono-, or unphosphorylated forms were used to study the binding of cellular proteins from human Jurkat T cells to these signal transduction motifs. The protein tyrosine kinase ZAP-70 bound specifically to all bisphosphorylated peptides but not to the mono- or unphosphorylated peptides. In contrast, Shc, phosphatidylinositol 3-kinase (P13K), Grb2, and Ras-GTPase activating protein (GAP) bound with different affinities to the bis- or monophosphorylated peptides, while the Src family protein tyrosine kinase (PTK) Fyn did not bind specifically to any of the tested peptides. The different preferences of the studied signaling molecules for distinct ITAMs, and in particular the binding of some of them preferentially to monophosphorylated peptides, suggests that the TCR-ζ may bind multiple signaling molecules with each ITAM binding a unique set of such molecules. In addition, partial phosphorylation of the ITAMs may result in recruitment of different proteins compared to double phosphorylation. This may be crucial for coupling of the TCR to various effector functions under different conditions of receptor triggering. © 1996 Wiley-Liss, Inc. 相似文献