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At least 973 records · Page 54Linked to original sources
PubMed1997

Cyclic AMP regulation of mouse proline-rich protein gene expression: isoproterenol induction of AP-1 transcription factors in parotid glands.

Proline-rich protein mRNAs are increased dramatically in the salivary glands of rats, mice, and hamsters upon treatment with the beta-agonist isoproterenol. Sequence comparisons between mice and hamster proline-rich protein genes identified conserved regions upstream from the transcription start site. Reporter plasmids containing these 5'-flanking sequences from a mouse proline-rich protein gene, MP2, were constructed and tested for transcriptional regulation by cAMP. Transient transfection experiments in mouse L-M cells showed that the upstream region -702 to -322 bp relative to the transcription start site is sufficient to confer cAMP induction on a heterologous promoter. Multiple copies of the AP-1 sequence elements within this region (-625 to -551) mediate the cAMP transcriptional response of reporter gene expression in L-M cells. L-M cell nuclear proteins and purified human c-jun protein bind to these upstream elements as determined by DNase I footprint analysis. Nuclear proteins isolated from mouse parotid glands protected the consensus AP-1 binding site 5'-TGAGTCA-3' (-592 to -586). The nuclear proteins interacting at this site were increased about sixfold in glands isolated from isoproterenol-treated mice when compared with glands from untreated mice. These results suggest that induction of AP-1 transcription factors in the parotid gland control the upregulation of some mouse salivary proline-rich proteins.

Adrenergic beta-Agonists↗
PubMed1994

Proline mutations on the S4 segment of rat brain sodium channel II.

We have studied S4-proline mutants of the rat brain sodium channel II. In mutant A224P one proline was added on the S4 segment of repeat I, and in mutant P1313V a proline was removed from the segment S4 of the repeat II. In both mutants, the activation curve was shifted to more positive potentials, without changing the steepness of the voltage dependence. The time course of inactivation, consisting of two exponential components, was similar in the wild type and in mutant A224P. Differently, the decay of the current in mutant P1313V had only one component, with a time constant similar to that of the fast component of wild type channels. This change in kinetics was accompanied in mutant P1313V by a change in the voltage dependence of the apparent steady-state inactivation. We conclude that the addition or deletion of prolines in segment S4 does not affect significantly the activation of sodium channels, but alters their mode of inactivation.

Animals↗
PubMed1994

Characterization of the proline-rich region of mouse MAPKAP kinase 2: influence on catalytic properties and binding to the c-abl SH3 domain in vitro.

The primary structure of mouse MAP kinase-activated protein (MAPKAP) kinase 2 contains a proline-rich N-terminal region which might function as a src-homology 3 (SH3) domain-binding motif in vivo. To demonstrate the ability of this region to bind SH3 domains, we analyzed the interaction of the SH3 domain of the protein tyrosine kinase c-abl with MAPKAP kinase 2. It is demonstrated, that the proline-rich region specifically binds c-abl-SH3 domain in vitro. Furthermore, it is shown, that deletion of this proline-rich region does not significantly influence the substrate binding properties of the enzyme when analyzed with the substrate small heat shock protein Hsp25. The data suggest that the proline-rich region of MAPKAP kinase 2 could interact with proteins containing SH3-domains also in vivo regulating its cellular localization and/or modulating its enzymatic properties.

Amino Acid Sequence↗
PubMed1995

A hypothetical structural role for proline residues in the flanking segments of protein-protein interaction sites.

An examination of more than 1600 protein-protein interaction sites indicated that proline is the residue most commonly found near interaction sites. A structural role is distinguished for these proline residues in the flanking segments of protein-protein interaction sites. The unique nature of proline helps protect the integrity and present the sites, thus promoting protein-protein interactions. A novel approach to the design and development of potent peptide drugs and a simple predictive method to identify protein-protein interaction sites directly from the amino acid sequence have been developed based on this finding. The recognition of this structural role for proline has strong implications for protein chemistry and protein engineering.

Amino Acid Sequence↗
PubMed2000

Proline alleviates salt-stress-induced enhancement in ribulose-1, 5-bisphosphate oxygenase activity.

Sodium chloride enhanced oxygenase activity while curtailing carboxylase activity of Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase; EC 4.1.1.39) purified to electrophoretic homogeneity. Exposure to 200 mM NaCl brought about an increase in the potential of Rubisco to oxygenate RuBP by over 50%. On the other hand, proline suppressed both oxygenase as well as carboxylase activities of Rubisco. Interestingly, proline-induced suppression in oxygenase activity was significantly higher than that of carboxylase activity. Most amazingly, salt-stress-induced enhancement in oxygenase activity was fully alleviated by proline even when present at a concentration as low as 50 mM. The findings presented in this communication clearly demonstrate for the first time that stress-induced proline accumulation might have a critical role in lowering the loss in fixed carbon by curtailing salt-stress-promoted enhancement in oxygenase activity of Rubisco.

Fabaceae↗
PubMed1997

The rate of isomerisation of peptidyl-proline bonds as a probe for interactions in the physiological denatured state of chymotrypsin inhibitor 2.

There are four peptidyl-proline bonds in the 64-residue protein chymotrypsin inhibitor 2 (CI2), all of which are in the trans conformation in the native structure. The isomerisation of one or more of these peptidyl-proline bonds to the cis conformation in the denatured state gives rise to heterogeneity, leading to both fast and slow-folding species. The refolding of the fast-folding species, which has all trans peptidyl-proline bonds, is much faster than that of the slow-folding species, which have one or more cis peptidyl-proline bonds. In CI2, the slow-folding species can be classified into two groups by their rates of refolding, temperature-dependence, pH-dependence and [GdmCl]-dependence of the rate constants and the effect of peptidyl-prolyl isomerase on the rate constants. The replacement of Pro6 by Ala removes one of the slow refolding phases, suggesting that the cis peptidyl-Pro6 conformation is solely responsible for one of the slow-folding species. Pro6 is located in a region of the protein where non-random interactions have been found in a series of N-terminal fragments of CI2 (residues 1 to 13, 1 to 25, 1 to 28 and 1 to 40). In addition, NMR studies on a mutant fragment, (1-40)T3A, have confirmed that this non-native interaction is associated with the bulky side-chain of Trp5. The atypical rate of cis to trans isomerisation of the peptidyl-Pro bond is indicative of the presence of a similar hydrophobic cluster in the physiological denatured state of intact CI2.

Amino Acid Isomerases↗
PubMed1998

Recognition of protein substrates by the prolyl isomerase trigger factor is independent of proline residues.

The trigger factor is associated with bacterial ribosomes and catalyzes proline-limited protein folding reactions. Its folding activity is very high and conserved in evolution, as shown for the homologous enzymes from Escherichia coli and Mycoplasma genitalium. The folding protein substrate (a variant of ribonuclease T1) binds with high affinity to the trigger factors, and permanently unfolded proteins are strong, competitive inhibitors. We used this inhibition to characterize the substrate binding sites of the trigger factors. Unfolded alpha-lactalbumin binds very tightly and inhibits the trigger factor from M. genitalium with a KI value of 50 nM. The binding of inhibitory proteins is independent of proline residues, as shown for unfolded tendamistat, which binds to the trigger factor with equal affinity in the presence and in the absence of its three proline residues. The good inhibition by a non-folding variant of ribonuclease T1 that lacks Pro39 showed that this proline, at which the catalysis of folding occurs, is dispensable for substrate binding. The trigger factors cannot catalyze prolyl isomerization when proteins are partially folded already. They preferentially recognize unstructured protein chains, which bind with high affinity to a site distinct from the catalytic prolyl isomerase center in the FKBP domain.

Catalysis↗
PubMed1998

Generation and the fate of C2, C3, and C4 reactive fragments formed in Maillard model systems of [13C]glucose and [13C]glycine or proline.

Model studies with pyrolysis/GC/MS using labeled [13C] glucoses with labeled [15N/13C]glycines and proline have indicated that the Maillard model systems consisting of glucose and glycine or proline generate similar C2, C3, C4 fragments such as acetic acid, and pyruvaldehyde. Furthermore, the labeling studies have enabled the identification of the origin of these reactive intermediates and their stable end-products such as N-acetylpyrrolidine, 1-(1'-pyrrolidinyl)-2-propanone amd 1-(1'-pyrrolidinyl)-2-butanone in proline model system and pyrazines and pyrazinones in glycine. In glycine model system, pyruvaldehyde and 2,3-butandione were found to be formed either from the degradation of the carbohydrate moiety (90 and 35%, respectively) or by an aldol-type interaction of glycine with alpha-ketoaldehydes. The same intermediates in proline system are formed exclusively from the carbohydrate degradation pathway.

Carbon Isotopes↗
PubMed1980

Molecular specificity of tubular reabsorption of L-proline. A microperfusion study in rat kidney.

In microperfusion experiments the reabsorption of 3H and 14C labelled L-proline by two recently defined transport systems (one with high capacity and low affinity, the other one having the opposite characteristics) was measured in vivo et situ on addition of several amino acids and some N-methylated derivatives. The high capacity system is apparently an unspecific system for neutral amino acids. The methylation of the amino group does not change the affinity to the system. The affinity decreases in the order phenylalanine > glutamine > alanine > proline, hydroxyproline > glycine. The low capacity system seems to be a specific reabsorption mechanism for imino acids like proline, hydroxyproline, sarcosine an N-methylalanine. Common neutral amino acids are not accepted. The different characteristics of both transport systems are also demonstrated by the finding that the affinity of phenylalanine for the high capacity system is about 5 times higher but its affinity for the low capacity system is about 50 times lower than the affinity for proline.

Absorption↗
PubMed1989

Characteristics of L-proline and sodium transport in renal brush border membranes isolated from 7-day-old and adult rats.

To explore the nature of differences in uptake by renal brush border vesicles from animals of different ages, vesicles were isolated from 7-day old and adult rats by a Mg-aggregation method. A number of criteria were compared in vesicles from the young and mature animals. The vesicles isolated from animals of both ages appear similar on electron microscopy, in response to osmotic changes, and in uptake kinetics for L-glucose. Despite these parameters which indicate no basic differences between the membranes of young and mature kidney, differences in proline and sodium handling are seen. When compared to the uptake pattern seen in vesicles from adult animals, the height of the sodium gradient-stimulated proline overshoot is diminished and sodium entry is faster in vesicles of the 7-day old rats. These are the same differences which were found in vesicles prepared by differential centrifugation from 7-day old animals. In addition, although sodium efflux was faster from vesicles of immature kidney and mirrored the faster sodium entry, proline efflux was slower. The data indicate a dissociation of proline and sodium fluxes in brush borders of the young rat kidney.

Aging↗
PubMed1999

A comparison of 15N proline and 13C leucine for monitoring protein biosynthesis in the skin.

The tracers L 15N-proline and L(1-13C)-leucine were used to explore the synthesis of skin proteins in vivo in rabbits. They orally received a single dose containing an equimolecular mixture of L(1-13C)-leucine and L 15N-proline. The changes in the amounts of these tracers in blood and skin were monitored for a total of 8 h. The data showed the appearance of the two tracers in blood within 15 min and their clearance in 8 h. They were both rapidly (15 min) incorporated into skin proteins, but more proline was incorporated than leucine. We therefore consider L 15N-proline to be a better tracer than L(1-13C)-leucine for studying protein metabolism in the skin.

Animals↗
PubMed1991

Dissecting the molecular mechanism of ion-solute cotransport: substrate specificity mutations in the putP gene affect the kinetics of proline transport.

Rare mutations that alter the substrate specificity of proline permease cluster in discrete regions of the putP gene, suggesting that they may replace amino acids at the active site of the enzyme. If putP substrate specificity mutations directly after the active site of proline permease, the mutants should show specific defects in the kinetics of proline transport. In order to test this prediction, we examined the kinetics of three putP substrate specificity mutants. One class of mutation increases the Km over 120 fold but only decreases the Vmax fourfold. Such Km mutants may be specifically defective in substrate recognition, thus identifying an amino acid critical for substrate binding. Another class of mutation decreases the Vmax 80-fold without changing the Km. Vmax mutants appear to alter the rate of substrate translocation without affecting the substrate binding site. The last class of mutation alters both the Km and Vmax of proline transport. These results indicate that substrate specificity mutations alter amino acids critical for Na+/proline symport.

Amino Acid Transport Systems, Neutral↗
PubMed1983

Hepatic proline after bile duct ligation in rats.

Since biliary hyperplasia of fascioliasis correlated with hepatic proline level, we examined the occurrence of a similar chemical stimulus during bile obstruction. Uptake of tritiated proline and glycine rose in both hepatocytes and a bile duct enriched cell fraction, following duct ligation in rats. The increased hepatic content of proline but not glycine suggests that proline has a role in post-obstructive biliary proliferation.

Animals↗
PubMed1985

Proline is required for the stimulation of DNA synthesis in hepatocyte cultures by EGF.

Epidermal growth factor (EGF) has been shown to stimulate DNA synthesis in rat parenchymal hepatocytes both in vivo in vitro. We report here that this response in vitro is dependent on the amino acids present in the media. Of all the amino acids, proline has the strongest effect. The response to EGF is absent without proline and none of the other amino acids can substitute for it. Added proline (1 mM) to the media caused the labeling index to increase from 11% to 55% in the presence of 50 ng/ml EGF and insulin. In the presence of proline, small additional increases of the EGF effect on DNA synthesis were stimulated by phenylalanine and tyrosine.

Animals↗
PubMed1992

A biosensor for L-proline determination by use of immobilized microbial cells.

A biosensor to quantify L-proline within 10(-5)-10(-3) mole/L concentration is described. Immobilized Pseudomonas sp. cells grown in a medium containing L-proline as the only source of carbon and nitrogen were used to create the biosensor. The cells oxidized L-proline specifically consuming O2 and did not react with other amino acids and sugars. The change in oxygen concentration was detected with a Clark oxygen membrane electrode. The cells were immobilized by entrapment in polyvinyl alcohol (PVA) cryogel. The resultant biocatalyst had a high mechanical strength and retained its L-proline-oxidizing ability for at least two months.

Adenosine Triphosphate↗
PubMed2005

T-cell recognition of HLA-DQ2-bound gluten peptides can be influenced by an N-terminal proline at p-1.

Recent research has implicated a large number of gluten-derived peptides in the pathogenesis of celiac disease, a preponderantly HLA-DQ2-associated disorder. Current evidence indicates that the core of some of those peptides is ten amino acids long, while HLA class II normally accommodates nine amino acids in the binding groove. We have now investigated this in detail, using gluten-specific T-cell clones, HLA-DQ2-specific peptide-binding assays and molecular modelling. T-cell recognition of both a gamma-gliadin peptide and a low-molecular-weight glutenin peptide was found to be strictly dependent on a ten-amino acids-long peptide. Subsequent peptide-binding studies indicated that the glutenin peptide bound in a conventional p1/p9 register, with an additional proline at p-1. Testing of substitution analogues demonstrated that the nature of the amino acid at p-1 strongly influenced T-cell recognition of the peptide. Moreover, molecular modelling confirmed that the glutenin peptide binds in a p1/p9 register, and that the proline at p-1 points upward towards the T-cell receptor. Database searches indicate that a large number of potential T-cell stimulatory gluten peptides with an additional proline at relative position p-1 exist, suggesting that the recognition of other gluten peptides may depend on this proline as well. This knowledge may be of importance for the identification of additional T-cell stimulatory gluten peptides and the design of a peptide-based, tolerance-inducing therapy.

Amino Acid Sequence↗
PubMed2005

A rust-inducible gene from flax (fis1) is involved in proline catabolism.

A gene fis1 from flax (Linum usitatissimum), which is induced in mesophyll cells at the site of rust (Melampsora lini) infection, is also expressed in vascular tissue, particularly in floral structures of healthy plants. This paper reports that the promoter controlling this expression is contained within 282 bp 5' to the coding region and that fis1 gene induction is specifically by the rust pathogen and not by other fungal pathogens or by wounding. The fis1 gene has 73% homology with an Arabidopsis gene which encodes delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDH) which is a part of the proline degradation pathway. Transgenic flax plants that either over-express fis1 or show reduced fis1 expression due to RNA-mediated gene silencing have an unaltered morphology. However, plants with reduced fis1 expression have markedly increased sensitivity to exogenous proline and show alteration in epidermal cell morphology, callose deposition and the production of hydrogen peroxide during proline-induced death. These lines, which show a biologically significant level of fis1 suppression, have an unaltered reaction to either virulent or avirulent rust infections, as do fis1 over-expression lines. These data indicate that the fis1 gene plays a role in proline metabolism and most likely encodes for a P5CDH enzyme. However, the precise role of fis1 and P5C catabolism in the development of rust disease remains unclear.

1-Pyrroline-5-Carboxylate Dehydrogenase↗
PubMed2006

Two tobacco proline dehydrogenases are differentially regulated and play a role in early plant development.

Proline dehydrogenase is the rate-limiting enzyme in proline degradation and serves important functions in the stress responses and development of plants. We isolated two tobacco proline dehydrogenases, NtPDH1 and NtPDH2, in the course of screening for genes upregulated in stressed tobacco (Nicotiana tabacum) microspores. Expression analysis revealed that the two genes are differentially regulated. Under unstressed conditions, their steady-state transcript levels were similar in mature pollen and apical meristems, whereas NtPDH2 was expressed predominantly in vegetative organs, styles, and ovules. The expression of NtPDH1 was maintained at a constant low level during 24 h of dehydration, whereas NtPDH2 was upregulated within 1 h after the onset of stress and subsequently downregulated to undetectable levels. Differential and sustained expression was also found for the two enzymatic isoforms of Arabidopsis thaliana AtPDH. Silencing of the NtPDH genes by RNA interference using the CaMV 35S promoter led to increased proline contents, decreased seed set, delayed seed germination and retarded seedling development pointing towards an important function of at least one of the two NtPDH genes during plant reproductive development.

Amino Acid Sequence↗