Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “polyamines”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,405 records · Page 78Linked to original sources
PubMed1980

Spontaneous and polyamine-induced formation of filamentous polymers from soluble fibronectin.

Fibronectin is a high-molecular-weight glycoprotein present in a soluble form in plasma and in other body fluids and as insoluble protein in connective tissue matrix. This study reports that soluble fibronectin is polymerized into filamentous structures and that polyamines stimulate this process and precipitate fibronectin. Fibronectin purified from human plasma under non-denaturing conditions appeared after negative staining as non-globular extended structures in the electron microscope. During storage of purified fibronectin at +4 degrees C, in particular a low ionic strength, increasing amounts of the protein appeared as protein filaments. These filaments had a diameter of 2--3 nm and a length of up to several micrometers. The filaments also formed bundles of variable thickness, apparently through lateral association. These structures could also be visualized by phase-contrast microscopy. Polyamines, at a concentration of 1--5 mM and at a low ionic strength, induced a rapid, extensive polymerization of fibronectin into filamentous structures. The effect increased in the order putrescine less than spermidine less than spermine. Polyamine-induced precipitation of fibronectin was reversible upon removal of the polyamine. Fibronectin secreted by normal and by malignant cells could be fairly selectively precipitated from the culture medium with polyamines. The observed filamentous polymers of soluble fibronectin resemble the filamentous fibronectin-containing pericellular structures in fibroblast cultures and may provide a model for studies on the deposition of fibronectin in matrix form.

Chromatography, Agarose↗
PubMed1995

Interaction of polyamines with the Ca(2+)-binding protein parvalbumin.

The interaction of spermine, spermidine and putrescine with the Ca(2+)-binding protein, parvalbumin, was studied at pH 6 and 7, with the help of the intrinsic fluorescence properties of tryptophan and circular dichroic spectroscopy of the protein in the ultraviolet region. Polyamines bind to parvalbumin that is either Ca(2+)-free or partially saturated with Ca2+, as indicated by a change in the emission maximum and intensity of tryptophan fluorescence. The binding affinities for the interactions are about 4 mM, 8 mM and > 20 mM for spermine, spermidine and putrescine, respectively. No alterations in fluorescence properties were detected when the polyamines were added to fully Ca(2+)-bound parvalbumin. An increase in the ellipticity of the circular dichroic spectrum in the region where tryptophan absorbs was observed when polyamines were added to Ca(2+)-free parvalbumin. This finding indicates that polyamine binding affects the segment of the protein where tryptophan is located. Based on these results it is postulated that polyamines bind to the Ca(2+)-free or partially saturated parvalbumin and stabilize its structure.

Animals↗
PubMed1986

Effects of polyamines on proline endopeptidase activity in rat brain.

The in vitro effects of polyamines on the activity of proline endopeptidase (PEPase) in rat brain cytosol, which contains an endogenous PEPase inhibitor, have been studied. Of the three amines tested (spermine, spermidine, and putrescine), spermine and spermidine markedly enhanced the enzyme activity in brain cytosol. At 6.25 mM spermine or 25 mM spermidine, a 13- or 14-fold enhancement of the enzyme activity was observed. When Mg2+ was used, an approximately fourfold enhancement of the enzyme activity was observed at 50 mM. The enhancement produced by spermine or spermidine was unaffected by Mg2+ up to 50 mM. The activity of purified PEPase was only slightly affected by each polyamine, but it was inhibited 50% by 50 mM Mg2+. On the other hand, 50% inhibition of the enzyme produced by the purified PEPase inhibitor (Mr 7,000: Ki 0.67 mM) was completely restored by addition of 0.7 mM spermine, 3.5 mM spermidine, or 28 mM putrescine. This restoration of inhibition by polyamines was reversed by increasing the inhibitor concentration. These data suggest that polyamines effectively reverse the inhibition of PEPase by its endogenous inhibitor by the reversible formation of a kinetically significant complex. The possible functions of polyamines in the regulation of PEPase in vivo are discussed.

Animals↗
PubMed1989

Blood-brain barrier breakdown in cold-injured brain is linked to a biphasic stimulation of ornithine decarboxylase activity and polyamine synthesis: both are coordinately inhibited by verapamil, dexamethasone, and aspirin.

An early increase in ornithine decarboxylase (ODC) activity and polyamine levels in rat cerebral capillaries was previously implicated in the mediation of blood-brain barrier (BBB) breakdown in cold-injured brain. A time course study in rat cerebrum indicated that cold injury evokes a biphasic increase in ODC activity and polyamine levels in perilesional cortex. ODC activity rose sharply (fourfold) within 1 min, remained elevated for 5 min, and then returned to the basal level by 10 min. A transient rise in polyamine concentration followed in the rank order of putrescine greater than spermidine greater than spermine. A secondary rise in ODC activity commenced in perilesional tissue at 2-6 h and peaked (8.8-fold) at 48 h. Major increases in the content of putrescine (330%), spermidine (103%), and spermine (50%) developed at 48-72 h. alpha-Difluoromethylornithine (DFMO), a specific irreversible inhibitor of ODC, suppressed the evoked increase in ODC activity and abolished the associated increase in content of polyamines, findings indicating that the accumulation of polyamines in cryoinjured brain reflects enhanced synthesis resulting from an ODC-mediated increase in putrescine content. Cycloheximide and actinomycin D were without effect on the early increase in ODC activity but inhibited the delayed increase in ODC activity, an observation suggesting that the initial increase in activity reflects an activation of a cryptic ODC via a posttranslational process, whereas the delayed increase in activity results from ODC synthesis mainly under transcriptional control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Polyamine metabolism in experimental brain tumors of rat.

Biosynthesis and accumulation of the polyamines putrescine, spermidine, and spermine are closely associated with cellular growth processes. We examined polyamine levels and the activity of their first rate-limiting enzyme, ornithine decarboxylase (ODC), in stereotactically induced experimental gliomas of the rat brain 1 and 2 weeks after implantation. Regional ODC activity and polyamine levels were determined in the tumor and in the ipsi- and contralateral striatum, white matter, and cerebral cortex. In the tumor, both ODC activity and polyamine levels markedly increased with progressive tumor growth, as compared to those in the white matter of the opposite hemisphere. In the peritumoral brain tissue, ODC activity did not change, but there was a marked increase of putrescine and, to a lesser degree, of spermidine and spermine almost throughout the whole ipsilateral hemisphere. ODC activity, therefore, seems to be a reliable marker of neoplastic growth in the brain, which may be of use for new clinical concepts of the diagnosis and therapy of brain tumors. The more diffuse distribution of polyamines, however, may be associated with the formation and spreading of edema, which would explain some of the biological effects of tumors on distant brain tissue.

Animals↗
PubMed1993

Induction of ornithine decarboxylase by N-methyl-D-aspartate receptor activation is unrelated to potentiation of glutamate excitotoxicity by polyamines in cerebellar granule neurons.

Polyamines positively modulate the activity of the N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors. The concentration of polyamines in the brain increases in certain pathological conditions, such as ischemia and brain trauma, and these compounds have been postulated to play a role in excitotoxic neuronal death. In primary cultures of rat cerebellar granule neurons, exogenous application of the polyamines spermidine and spermine (but not putrescine) potentiated the delayed neurotoxicity elicited by NMDA receptor stimulation with glutamate. Furthermore, both toxic and nontoxic concentrations of glutamate stimulated the activity of ornithine decarboxylase (ODC)--the key regulatory enzyme in polyamine synthesis--and increased the concentration of ODC mRNA in cerebellar granule neurons but not in glial cells. Glutamate-induced ODC activation but not neurotoxicity was blocked by the ODC inhibitor difluoromethylornithine. Thus, high extracellular polyamine concentrations potentiate glutamate-triggered neuronal death, but the glutamate-induced increase in neuronal ODC activity may not play a determinant role in the cascade of intracellular events responsible for delayed excitotoxicity.

Animals↗
PubMed1986

Tetrodotoxin-sensitive, K+-induced relaxation of guinea-pig isolated trachealis in the presence of Ca2+-entry blocking drugs, Ca2+-free solution and after polyamine exposure.

We have previously observed a paradoxical relaxant effect of K+ on guinea-pig isolated trachealis after exposure to polyamines. The purpose of the present study was to evaluate whether the relaxation involved a reduction in the entry of extracellular Ca2+. We therefore investigated the effect of K+ in the presence of Ca2+-entry blocking drugs and in the presence of Ca2+-free solution. In the presence of nifedipine (10(-5) M), verapamil (10(-5) M) or diltiazem (10(-5) M), K+ (30 mM) induced relaxation of the trachealis muscle. The relaxation to K+ was not blocked by ouabain (10(-6) M), propranolol (10(-6) M), or indomethacin (10(-6) M). A relaxation in response to K+ was also observed in Ca2+-free solution, (with tone induced by methacholine), an effect not blocked by propranolol or ouabain. Tetraethylammonium (30 mM) (TEA), which ordinarily evokes contractile responses, induced trachealis relaxation in the presence of verapamil or nifedipine. The relaxation was unaltered by ouabain or propranolol. Tetrodotoxin (10(-6) M) (TTX) blocked 65% of the K+-induced relaxation in the presence of nifedipine and 100% of K+-induced relaxation either in a Ca2+-free solution or after polyamine exposure. TTX was without effect on TEA-induced relaxation after Ca2+-entry blocking drugs. Atropine (10(-6) M) or hexamethonium (10(-6) M) did not affect K+-induced relaxation after polyamine exposure. The concentration-response curve for K+-induced contraction in normal modified Krebs-Henseleit solution was shifted to the left by TTX. 8 It is concluded: (a) K+ has a direct effect on the trachealis causing contraction and an indirect effect, mediated by neurotransmitter release, causing relaxation. This latter effect is exposed when the direct effect is inhibited by Ca2+-entry blocking drugs, Ca2+-free solution or polyamine exposure; the indirect effect is non-adrenergic, non-cholinergic and not via ganglionic transmission; (b) the TEAinduced relaxation and a component of the K+-induced relaxation after Ca2+ blocking drugs cannot be explained by neurotransmitter release; (c) polyamines may act as naturally occurring Ca2+ antagonists.

Animals↗
PubMed1994

Effects of arginine, S-adenosylmethionine and polyamines on nerve regeneration.

INTRODUCTION: Axon growth and axon regeneration are complex processes requiring an adequate supply of certain metabolic precursors and nutrients. MATERIAL AND METHODS: This article reviews the studies examining some of the processes of protein modification fundamental to both nerve regeneration and to the continuous and adequate supply of specific factors such as arginine, S-adenosylmethionine and polyamines. RESULTS: The process of arginylation notably increases following nerve injury and during subsequent regeneration of the nerve, with the most likely function of arginine-modification of nerve proteins being the degradation of proteins damaged through injury. It appears that defective methyl group metabolism may be one of the leading causes of demyelination, as suggested by the observation of reduced cerebrospinal fluid concentrations of s-adenosylmethionine (SAMe) and 5-methyltetrahydrofolate, the key metabolites in methylation processes, in patients with a reduction in myelination of corticospinal tracts. Polyamine synthesis, which depends strongly on the availability of both SAMe and arginine, markedly increases in neurons soon after an injury. This "polyamine-response" has been found to be essential for the survival of the parent neurons after injury to their axons. Polyamines probably exert their effects through involvement in DNA, RNA and protein synthesis, or through post-translational modifications that are indicated as the most relevant events of the "axon reaction." CONCLUSIONS: Nerve regeneration requires the presence of arginine, s-adenosylmethionine, and polyamines. Further studies are needed to explore the mechanisms involved in these processes.

Arginine↗
PubMed2005

Nuclear aggregates of polyamines are supramolecular structures that play a crucial role in genomic DNA protection and conformation.

In a previous study we showed that natural polyamines interact in the nuclear environment with phosphate groups to form molecular aggregates [nuclear aggregates of polyamines (NAPs)] with estimated molecular mass values of 8000, 4800 and 1000 Da. NAPs were found to interact with genomic DNA, influence its conformation and interfere with the action of nucleases. In the present work, we demonstrated that NAPs protect naked genomic DNA from DNase I, whereas natural polyamines (spermine, spermidine and putrescine) fail to do so. In the context of DNA protection, NAPs induced noticeable changes in DNA conformation, which were revealed by temperature-dependent modifications of DNA electrophoretic properties. In addition, we presented, for NAPs, a structural model of polyamine aggregation into macropolycyclic compounds. We believe that NAPs are the sole biological forms by which polyamines efficiently protect genomic DNA against DNase I, while maintaining its dynamic structure.

Cell Nucleus↗
PubMed2002

Interaction between polyamines and bacterial outer membranes as investigated with ion-selective electrodes.

We analyzed the interaction between polyamines and the outer membrane of Escherichia coli cells using potentiometric measurements with Ca(2+), tetraphenylphosphonium (TPP(+)), and K(+) electrodes. The Ca(2+) electrode was used to examine the ability of the polyamines to release Ca(2+) from the outer membrane. The TPP(+) electrode was used to examine the ability to permeabilize the outer membrane, since the uptake of TPP(+) was enhanced when the permeability barrier of the outer membrane was disrupted. The K(+) electrode was used to examine permeabilization in the cytoplasmic membrane by monitoring the efflux of K(+) in cytosol. Although Ca(2+) release was remarkably enhanced by increasing the number of amino groups in polyamines, no TPP(+) uptake was observed with polyamines of a simple structure, such as ethylenediamine, spermidine, and spermine. TPP(+) uptake was observed when appropriate lipophilic moieties were further attached to the polyamines with three or four amino groups, indicating that the existence of bulky moieties as well as the number of amino groups is important to induce outer membrane permeabilization. Thus, 1-naphthylacetylspermine and N,N'-bis[6-[[(2-methoxyphenyl)methyl]amino]hexyl]-1,8-octanediamine (methoctramine) were especially effective in increasing the permeability of the outer membrane of E. coli cells, being comparable to polymyxin B nonapeptide, a well-known cationic peptide showing such action.

Anti-Bacterial Agents↗
PubMed2005

3-Aminooxy-1-aminopropane and derivatives have an antiproliferative effect on cultured Plasmodium falciparum by decreasing intracellular polyamine concentrations.

The intraerythrocytic development of Plasmodium falciparum correlates with increasing levels of the polyamines putrescine, spermidine, and spermine in the infected red blood cells; and compartmental analyses revealed that the majority is associated with the parasite. Since depletion of cellular polyamines is a promising strategy for inhibition of parasite proliferation, new inhibitors of polyamine biosynthesis were tested for their antimalarial activities. The ornithine decarboxylase (ODC) inhibitor 3-aminooxy-1-aminopropane (APA) and its derivatives CGP 52622A and CGP 54169A as well as the S-adenosylmethionine decarboxlyase (AdoMetDC) inhibitors CGP 40215A and CGP 48664A potently affected the bifunctional P. falciparum ODC-AdoMetDC, with K(i) values in the low nanomolar and low micromolar ranges, respectively. Furthermore, the agents were examined for their in vitro plasmodicidal activities in 48-h incubation assays. APA, CGP 52622A, CGP 54169A, and CGP 40215A were the most effective, with 50% inhibitory concentrations below 3 microM. While the effects of the ODC inhibitors were completely abolished by the addition of putrescine, growth inhibition by the AdoMetDC inhibitor CGP 40215A could not be antagonized by putrescine or spermidine. Moreover, CGP 40215A did not affect the cellular polyamine levels, indicating a mechanism of action against P. falciparum independent of polyamine synthesis. In contrast, the ODC inhibitors led to decreased cellular putrescine and spermidine levels in P. falciparum, supporting the fact that they exert their antimalarial activities by inhibition of the bifunctional ODC-AdoMetDC.

Adenosylmethionine Decarboxylase↗
PubMed1999

Control of filament formation in Candida albicans by polyamine levels.

Candida albicans, the most common fungal pathogen, regulates its cellular morphology in response to environmental conditions. The ODC gene, which encodes ornithine decarboxylase, a key enzyme in polyamine biosynthesis, was isolated and disrupted. Homozygous null Candida mutants behaved as polyamine auxotrophs and grew exclusively in the yeast form at low polyamine levels (0.01 mM putrescine) under all conditions tested. An increase in the polyamine concentration (10 mM putrescine) restored the capacity to switch from the yeast to the filamentous form. The strain with a deletion mutation also showed increased sensitivity to salts and calcofluor white. This Candida odc/odc mutant was virulent in a mouse model. The results suggest a model in which polyamine levels exert a pleiotrophic effect on transcriptional activity.

Alleles↗
PubMed2006

Involvement of potD in Streptococcus pneumoniae polyamine transport and pathogenesis.

Polyamines such as putrescine, spermidine, and cadaverine are small, polycationic molecules that are required for optimal growth in all cells. The intracellular concentrations of these molecules are maintained by de novo synthesis and transport pathways. The human pathogen Streptococcus pneumoniae possesses a putative polyamine transporter (pot) operon that consists of the four pot-specific genes potABCD. The studies presented here examined the involvement of potD in polyamine transport and in pneumococcal pathogenesis. A potD-deficient mutant was created in the mouse-virulent serotype 3 strain WU2 by insertion duplication mutagenesis. The growth of the WU2DeltapotD mutant was identical to that of the wild-type strain WU2 in vitro in rich media. However, WU2DeltapotD possessed severely delayed growth compared to wild-type WU2 in the presence of the polyamine biosynthesis inhibitors DFMO (alpha-dimethyl-fluoroornitithine) and MGBG [methylgloxal-bis (guanyl hydrazone)]. The mutant strain also showed a significant attenuation in virulence within murine models of systemic and pulmonary infection regardless of the inoculation route or location. These data suggest that potD is involved in pneumococcal polyamine transport and is important for pathogenesis within various infection models.

Animals↗
PubMed1990

Acquisition of polyamines by the obligate intracytoplasmic bacterium Rickettsia prowazekii.

Both the polyamine content and the route of acquisition of polyamines by Rickettsia prowazekii, an obligate intracellular parasitic bacterium, were determined. The rickettsiae grew normally in an ornithine decarboxylase mutant of the Chinese hamster ovary (C55.7) cell line whether or not putrescine, which this host cell required in order to grow, was present. The rickettsiae contained approximately 6 mM putrescine, 5 mM spermidine, and 3 mM spermine when cultured in the presence or absence of putrescine. Neither the transport of putrescine and spermidine by the rickettsiae nor a measurable rickettsial ornithine decarboxylase activity could be demonstrated. However, we demonstrated the de novo synthesis of polyamines from arginine by the rickettsiae. Arginine decarboxylase activity (29 pmol of 14CO2 released per h per 10(8) rickettsiae) was measured in the rickettsiae growing within their host cell. A markedly lower level of this enzymatic activity was observed in cell extracts of R. prowazekii and could be completely inhibited with 1 mM difluoromethylarginine, an irreversible inhibitor of the enzyme. R. prowazekii failed to grow in C55.7 cells that had been cultured in the presence of 1 mM difluoromethylarginine. After rickettsiae were grown in C55.7 in the presence of labeled arginine, the specific activities of arginine in the host cell cytoplasm and polyamines in the rickettsiae were measured; these measurements indicated that 100% of the total polyamine content of R. prowazekii was derived from arginine.

Animals↗
PubMed1996

Polyamines decrease Escherichia coli outer membrane permeability.

The permeability of the outer membranes of gram-negative bacteria to hydrophilic compounds is mostly due to the presence of porin channels. We tested the effects of four polyamines (putrescine, cadaverine, spermidine, and spermine) on two processes known to depend on intact porin function: fluxes of beta-lactam antibiotics in live cells and chemotaxis. In both cases, inhibition was observed. Measurements of the rate of permeation of cephaloridine and of chemotaxis in swarm plates and capillary assays were used to determine the concentration dependence of this modulation. The effective concentration ranges depended on the nature of the polyamine and varied from submillimolar for spermine to tens of millimolar for cadaverine. Both OmpC and OmpF porins were inhibited, although the effects on OmpC appeared to be milder. These results are in agreement with our observations that polyamines inhibit porin-mediated ion fluxes in electrophysiological experiments, and they suggest that a low-affinity polyamine binding site might exist in these porins. These results reveal the potential use of porins as targets for blocking agents and suggest that polyamines may act as endogenous modulators of outer membrane permeability.

Biogenic Polyamines↗
PubMed1965

EFFECT OF ETHAMBUTOL ON NUCLEIC ACID METABOLISM IN MYCOBACTERIUM SMEGMATIS AND ITS REVERSAL BY POLYAMINES AND DIVALENT CATIONS.

Forbes, M. (Lederle Laboratories Division, Pearl River, N.Y.), N. A. Kuck, and E. A. Peets. Effect of ethambutol on nucleic acid metabolism in Mycobacterium smegmatis and its reversal by polyamines and divalent cations. J. Bacteriol. 89:1299-1305. 1965.-Mycobacterium smegmatis, harvested from cultures inhibited by ethambutol and then suspended in drug-free medium, exhibited a prolonged lag before growth resumed. Polyamines and magnesium ions shortened this lag. Polyamines and magnesium added to the culture increased the minimal inhibitory concentration of the drug and reversed the inhibitory effect of the drug, even when added after the drug had already inhibited growth. When ethambutol was added to a culture in its exponential phase of growth, synthesis of protein and deoxyribonucleic acid (DNA), as measured by incorporation of S(35) and P(32), continued for 3 hr at a rate slightly less than in the control cells and then essentially ceased. Synthesis of ribonucleic acid (RNA) was depressed, but it proceeded even after protein synthesis had ceased. Even though the synthesis of RNA continued, the net RNA decreased, and inhibited cells became deficient in RNA. Polyamines and divalent cations, which reverse the inhibitory effect of the drug, have been reported to be involved in nucleic acid turnover. These considerations suggested that ethambutol may exert its inhibitory effect by interfering with a function of cellular polyamines and divalent cations in RNA metabolism.

Amines↗
PubMed2001

Branched polyamines cure prion-infected neuroblastoma cells.

Branched polyamines, including polyamidoamine and polypropyleneimine (PPI) dendrimers, are able to purge PrP(Sc), the disease-causing isoform of the prion protein, from scrapie-infected neuroblastoma (ScN2a) cells in culture (S. Supattapone, H.-O. B. Nguyen, F. E. Cohen, S. B. Prusiner, and M. R. Scott, Proc. Natl. Acad. Sci. USA 96:14529-14534, 1999). We now demonstrate that exposure of ScN2a cells to 3 microg of PPI generation 4.0/ml for 4 weeks not only reduced PrP(Sc) to a level undetectable by Western blot but also eradicated prion infectivity as determined by a bioassay in mice. Exposure of purified RML prions to branched polyamines in vitro disaggregated the prion rods, reduced the beta-sheet content of PrP 27-30, and rendered PrP 27-30 susceptible to proteolysis. The susceptibility of PrP(Sc) to proteolytic digestion induced by branched polyamines in vitro was strain dependent. Notably, PrP(Sc) from bovine spongiform encephalopathy-infected brain was susceptible to PPI-mediated denaturation in vitro, whereas PrP(Sc) from natural sheep scrapie-infected brain was resistant. Fluorescein-labeled PPI accumulated specifically in lysosomes, suggesting that branched polyamines act within this acidic compartment to mediate PrP(Sc) clearance. Branched polyamines are the first class of compounds shown to cure prion infection in living cells and may prove useful as therapeutic, disinfecting, and strain-typing reagents for prion diseases.

Humans↗
PubMed2001

Screening for modulators of spermine tolerance identifies Sky1, the SR protein kinase of Saccharomyces cerevisiae, as a regulator of polyamine transport and ion homeostasis.

Although most cells are capable of transporting polyamines, the mechanism that regulates polyamine transport in eukaryotes is still largely unknown. Using a genetic screen for clones capable of restoring spermine sensitivity to spermine-tolerant mutants of Saccharomyces cerevisiae, we have demonstrated that Sky1p, a recently identified SR protein kinase, is a key regulator of polyamine transport. Yeast cells deleted for SKY1 developed tolerance to toxic levels of spermine, while overexpression of Sky1p in wild-type cells increased their sensitivity to spermine. Expression of the wild-type Sky1p but not of a catalytically inactive mutant restored sensitivity to spermine. SKY1 disruption results in dramatically reduced uptake of spermine, spermidine, and putrescine. In addition to spermine tolerance, sky1Delta cells exhibit increased tolerance to lithium and sodium ions but somewhat increased sensitivity to osmotic shock. The observed halotolerance suggests potential regulatory interaction between the transport of polyamines and inorganic ions, as suggested in the case of the Ptk2p, a recently described regulator of polyamine transport. We demonstrate that these two kinases act in two different signaling pathways. While deletion or overexpression of SKY1 did not significantly affect Pma1p activity, the ability of overexpressed Sky1p, Ptk1p, and Ptk2p to increase sensitivity to LiCl depends on the integrity of PPZ1 but not of ENA1.

Adenosine Triphosphatases↗