Biomedical subjects

T Wieland

Publications and source records attributed to T Wieland.

At least 19 recordsLinked to original sources

PubMed2000

Cell cycle-dependent coupling of the vasopressin V1a receptor to different G proteins.

Arginine vasopressin (AVP) regulates biological processes by binding to G protein-coupled receptors. In Swiss 3T3 fibroblasts, expressing the V(1a) subtype of vasopressin receptors, AVP mobilizes calcium from intracellular stores. In proliferating cells, the AVP-induced increase in intracellular calcium concentration ([Ca(2+)](i)) was mediated by G proteins of the G(q) family, which are insensitive to pertussis toxin (PTX) pretreatment of the cells. In quiescent cells, the AVP-induced increase in [Ca(2+)](i) was partially PTX-sensitive, suggesting an involvement of G(i) proteins. We confirmed this by photoaffinity labeling of G proteins in Swiss 3T3 cell membranes activated by AVP. In Swiss 3T3 cells arrested in the G(0)/G(1) phase of the cell cycle, the AVP-induced increase in [Ca(2+)](i) was also partially PTX-sensitive but was PTX-insensitive in cells arrested in other phases of the cell cycles. The blocking effect of PTX pretreatment in G(0)/G(1) cells was mimicked by microinjection of antisense oligonucleotides suppressing the expression of the Galpha(i3) subunits. These results were confirmed by microinjection of antibodies directed against the C terminus of G protein alpha-subunits. The data presented indicate that in Swiss 3T3 fibroblasts synchronized in the G(0)/G(1) phase of the cell cycle the V(1a) receptor couples to G(q/11) and G(i3) to activate the phospholipase C-beta, leading to release of intracellular calcium.

3T3 Cells↗

PubMed2000

The M3 muscarinic acetylcholine receptor expressed in HEK-293 cells signals to phospholipase D via G12 but not Gq-type G proteins: regulators of G proteins as tools to dissect pertussis toxin-resistant G proteins in receptor-effector coupling.

The M(3) muscarinic acetylcholine receptor (mAChR) expressed in HEK-293 cells couples to G(q) and G(12) proteins and stimulates phospholipase C (PLC) and phospholipase D (PLD) in a pertussis toxin-insensitive manner. To determine the type of G protein mediating M(3) mAChR-PLD coupling in comparison to M(3) mAChR-PLC coupling, we expressed various Galpha proteins and regulators of the G protein signaling (RGS), which act as GTPase-activating proteins for G(q)- or G(12)-type G proteins. PLD stimulation by the M(3) mAChR was enhanced by the overexpression of Galpha(12) and Galpha(13), whereas the overexpression of Galpha(q) strongly increased PLC activity without affecting PLD activity. Expression of the RGS homology domain of Lsc, which acts specifically on Galpha(12) and Galpha(13), blunted the M(3) mAChR-induced PLD stimulation without affecting PLC stimulation. On the other hand, overexpression of RGS4, which acts on Galpha(q)- but not Galpha(12)-type G proteins, suppressed the M(3) mAChR-induced PLC stimulation without altering PLD stimulation. We conclude that the M(3) mAChR in HEK-293 cells apparently signals to PLD via G(12)- but not G(q)-type G proteins and that G protein subtype-selective RGS proteins can be used as powerful tools to dissect the pertussis toxin-resistant G proteins and their role in receptor-effector coupling.

Carbachol↗

PubMed2000

Polarity exchange at the interface of regulators of G protein signaling with G protein alpha-subunits.

RGS proteins are GTPase-activating proteins (GAPs) for G protein alpha-subunits. This GAP activity is mediated by the interaction of conserved residues on regulator of G protein signaling (RGS) proteins and Galpha-subunits. We mutated the important contact sites Glu-89, Asn-90, and Asn-130 in RGS16 to lysine, aspartate, and alanine, respectively. The interaction of RGS16 and its mutants with Galpha(t) and Galpha(i1) was studied. The GAP activities of RGS16N90D and RGS16N130A were strongly attenuated. RGS16E89K increased GTP hydrolysis of Galpha(i1) by a similar extent, but with an about 100-fold reduced affinity compared with non-mutated RGS16. As Glu-89 in RGS16 is interacting with Lys-210 in Galpha(i1), this lysine was changed to glutamate for compensation. Galpha(i1)K210E was insensitive to RGS16 but interacted with RGS16E89K. In rat uterine smooth muscle cells, wild type RGS16 abolished G(i)-mediated alpha(2)-adrenoreceptor signaling, whereas RGS16E89K was without effect. Both Galpha(i1) and Galpha(i1)K210E mimicked the effect of alpha(2)-adrenoreceptor stimulation. Galpha(i1)K210E was sensitive to RGS16E89K and 10-fold more potent than Galpha(i1). Analogous mutants of Galpha(q) (Galpha(q)K215E) and RGS4 (RGS4E87K) were created and studied in COS-7 cells. The activity of wild type Galpha(q) was counteracted by wild type RGS4 but not by RGS4E87K. The activity of Galpha(q)K215E was inhibited by RGS4E87K, whereas non-mutated RGS4 was ineffective. We conclude that mutation of a conserved lysine residue to glutamate in Galpha(i) and Galpha(q) family members renders these proteins insensitive to wild type RGS proteins. Nevertheless, they are sensitive to glutamate to lysine mutants of RGS proteins. Such mutant pairs will be helpful tools in analyzing Galpha-RGS specificities in living cells.

Adenylyl Cyclases↗

PubMed2000

Pregnancy switches adrenergic signal transduction in rat and human uterine myocytes as probed by BKCa channel activity.

1. We used large conductance Ca2+-activated K+ (BKCa) channel activity as a probe to characterize the inhibitory/stimulatory G protein (Gi/Gs) signalling pathways in intact cells from pregnant (PM) and non-pregnant (NPM) myometrium. 2. Isoprenaline (10 microM) enhanced the outward current (Iout) in PM cells and inhibited Iout in NPM cells. Additional application of the alpha2-adrenoceptor (alpha2-AR) agonist clonidine (10 microM) further enhanced the isoprenaline-modulated Iout in PM cells but partially antagonized Iout in NPM cells. Clonidine alone did not affect Iout. The specific cAMP kinase (PKA) inhibitor H-89 (1 microM) abolished the effects of isoprenaline and clonidine. The specific BKCa channel blocker iberiotoxin (0.1 microM) inhibited Iout by approximately 80 %; the residual current was insensitive to isoprenaline. 3. Inhibition of Gi activity by either pertussis toxin or the GTPase activating protein RGS16 abolished inhibitory as well as stimulatory effects of clonidine on Iout. 4. Transducin-alpha, a scavenger of Gi betagamma dimers, converted the stimulatory action of clonidine on Iout into an inhibitory effect. Free transducin-betagamma enhanced both the stimulatory and the inhibitory effects of isoprenaline on Iout. 5. The results demonstrate that BKCa channel activity is a sensitive probe to follow adenylyl cyclase-cAMP-PKA signalling in myometrial smooth muscle cells. Both Gialpha-mediated inhibition and Gibetagamma-mediated stimulation can occur in the same cell, irrespective of pregnancy. It is speculated that the coupling between alpha2-AR and Gi proteins is more efficient during pregnancy and that Gibetagamma at high levels simply override the inhibitory action of Gi alpha.

Adenylyl Cyclases↗

PubMed2000

[Potential drug interactions and number of prescription drugs with special instructions at hospital discharge].

OBJECTIVE: Up to 6% of all hospitalizations are due to adverse drug reactions and 20% of these are caused by drug-drug interactions. There is only little information on the prescription frequency of drug-combinations with the potential to induce dangerous drug-drug interactions and drugs with the need for special patient instruction (e.g. inhalers). The aim of our study was to investigate the frequency of such drug prescriptions at hospital discharge. PATIENTS AND METHODS: In a retrospective, descriptive study drug prescriptions of 100 patients discharged consecutively from the department of internal medicine of a 300 bed-hospital were analysed. Possible drug-drug interactions were detected using a special computer program. Furthermore, the number of prescriptions warranting patient instruction such as anticoagulants, antidiabetics, hormones, immunosuppressive drugs, chemotherapeutics, antituberculotic and antiepileptic drugs as well as inhalatives and injections was recorded. RESULTS: The mean age of the 100 patients (61 men, 39 women) was 61.7 years, the mean duration of the hospital stay was 9.2 days. At discharge, patients took an average of 3.5 different drugs. Half of the patients were given drug-combinations with the potential for drug-drug interactions, whereby 5% were at risk for the development of interactions of severe and 42% of intermediate degree. All drug-combinations with potentially severe interactions were prescribed deliberately. 31% of all patients took medications with the need for special education, with inhalatives being the most frequent. The prescription of drugs with potential interactions and the necessity for special patient instruction was more frequent in the elderly. CONCLUSIONS: Drug-combinations with the potential of harmful interactions and drugs with the requirement for special patient instruction are frequently prescribed at hospital discharge. The frequency of prescribing these drugs increases with age. Detection of potentially dangerous drug-drug interactions is simplified by special computer programs. Careful patient instruction about the use of certain drugs is a key issue to improve patient compliance and to guarantee an optimal treatment effect.

Aged↗

PubMed2000

Apparent up-regulation of stimulatory G-protein alpha subunits in the pregnant human myometrium is mimicked by elevated smoothelin expression.

Sensitization of adenylyl cyclase (AC) by increased expression of large isoforms of the stimulatory G-protein Galpha(s) has been suggested as a mechanism that governs uterine quiescence during pregnancy. We quantified several components of the AC pathway in pregnant (P, n=21) and nonpregnant human myometria (NP, n=10). AC activity was approximately sevenfold higher in P than in NP under basal and stimulated conditions (MnCl(2)/GTP/GTP + isoproterenol). In addition, relative stimulation (% of basal) by 5'-guanosine-betagamma-iminotriphosphate and forskolin was twofold higher in P. beta-Adrenoceptor density was low and unaltered in P. Galpha(s) mRNA splice variants did not differ in P. Using antisera against different epitopes of Galpha(s) (carboxyl-/more amino-terminal), we found unchanged expression of Galpha(s) short and long (45, 47 kDa) in P. Two additional proteins in P (51, 59 kDa) were detectable only by the carboxyl-terminal antiserum and lacked GTP binding properties. The 59 kDa protein could be identified as a recently discovered cytoskeletal protein, smoothelin, which was 10-fold increased in P. These data indicate that the apparent up-regulation of large Galpha(s) species in P is mimicked by elevated smoothelin. Therefore, the increase in AC cannot be attributed to changes in Galpha(s)- or beta-adrenoreceptors. Epitope sharing between Galpha(s) and smoothelin should be considered in experiments on smooth muscle tissues.

5'-Nucleotidase↗

PubMed1999

Molecular characterization and module composition of P22-related Salmonella phage genomes.

Genomes of newly isolated Salmonella phages were analysed by comparison of their EcoRI restriction patterns and by hybridization. Characteristic hybridization probes from reference phages P22, ES18 and E. coli phage lambda were chosen. Four probes selected from the lysis region examined the dispersal of the lambdoid lysis genes. Other probes characterized were the replication genes and part of the structural genes. The complex immunity region was investigated by means of hybridization as well as biological tests. The results showed the relationship of the isolated phages to the P22 branch of the lambdoid phages and revealed their modular genome organization consisting of different proportions of P22-related sequences. DNA restriction patterns of phages released from Salmonella strains sampled in limited geographical areas were significantly less heterogeneous than those of phages released from the worldwide sampled SARA collection. The use of prophage restriction patterns as a tool for the typing of Salmonellae to support the epidemiologic classification of pathogenic strains is discussed.

Bacteriophage P22↗

PubMed1999

[Biliary ascariasis in the mountains].

Explore the source record for details and available documents.

Aged↗

PubMed1999

Regulators of G-protein signalling: a novel protein family involved in timely deactivation and desensitization of signalling via heterotrimeric G proteins.

In a variety of signalling pathways heterotrimeric guanine-nucleotide-binding proteins (G proteins) trigger physiological responses elicited by hormones, neurotransmitters and sensory stimuli. Receptor-induced GDP/GTP exchange activates G proteins by dissociating G-protein alpha-subunits from the betagamma-dimers. Both alpha-subunits and betagamma-dimers are involved in effector regulation. The deactivation of these active forms is controlled by the hydrolysis of GTP bound to alpha-subunits, allowing the inactive heterotrimer to reform. Termination of G-protein-mediated signalling in vivo is 10- to 100-fold faster than the in vitro rate of GTP hydrolysis by alpha-subunits, suggesting that in analogy to the GTPases of the Ras-superfamily, GTPase-activating proteins (GAPs) are required to achieve timely deactivation. Recently, members of a novel protein superfamily, known as "regulators of G-protein signalling" (RGS), were identified as potent GAPs for at least one subset of heterotrimeric G-protein alpha-subunits. In this review, we intend to discuss the proposed mechanism by which RGS proteins exert GAP activity for G-protein alpha-subunits as well as their specificities. The role of RGS proteins in desensitization and temporal resolution in certain signalling pathways will also be addressed.

Animals↗

PubMed1998

A comparative study on the frequency of prophages among natural isolates of Salmonella and Escherichia coli with emphasis on generalized transducers.

Several collections of natural isolates of the genus Salmonella and of the species Escherichia coli were studied for the release of viable temperate phages. The results indicated that functional prophage genomes may be a common constituent of all bacterial genomes of the investigated strains. About 99% of the Salmonella phages are capable of generalized transduction of chromosomal host markers and plasmids. The ratio of transducing E. coli phages is significantly lower.

Animals↗

PubMed1997

The Ca2+-dependent binding of calmodulin to an N-terminal motif of the heterotrimeric G protein beta subunit.

Ca2+ ion concentration changes are critical events in signal transduction. The Ca2+-dependent interactions of calmodulin (CaM) with its target proteins play an essential role in a variety of cellular functions. In this study, we investigated the interactions of G protein betagamma subunits with CaM. We found that CaM binds to known betagamma subunits and these interactions are Ca2+-dependent. The CaM-binding domain in Gbetagamma subunits is identified as Gbeta residues 40-63. Peptides derived from the Gbeta protein not only produce a Ca2+-dependent gel mobility shifting of CaM but also inhibit the CaM-mediated activation of CaM kinase II. Specific amino acid residues critical for the binding of Gbetagamma to CaM were also identified. We then investigated the potential function of these interactions and showed that binding of CaM to Gbetagamma inhibits the pertussis toxin-catalyzed ADP-ribosylation of Galphao subunits, presumably by inhibiting heterotrimer formation. Furthermore, we demonstrated that interaction with CaM has little effect on the activation of phospholipase C-beta2 by Gbetagamma subunits, supporting the notion that different domains of Gbetagamma are responsible for the interactions of different effectors. These findings shed light on the molecular basis for the interactions of Gbetagamma with Ca2+-CaM and point to the potential physiological significance of these interactions in cellular functions.

Adenosine Diphosphate Ribose↗

PubMed1997

[Pneumococcal vaccination--why so rare?].

Pneumococcal infections are common even in 1997 and are still responsible for high mortality rates particularly in groups at high risk. Because of increasing resistance of streptococcus pneumoniae against antibiotics the use of pneumococcal vaccination available so far could be an important preventive measure in particular in patients at high risk. This is demonstrated by means of some proper cases and the current literature.

Adult↗

PubMed1997

The retinal specific protein RGS-r competes with the gamma subunit of cGMP phosphodiesterase for the alpha subunit of transducin and facilitates signal termination.

In vertebrate photoreceptor cells, transducin mediates signaling between rhodopsin and cGMP phosphodiesterase by transiently binding its gamma subunit (PDEgamma). For the termination of signaling GTP hydrolysis by the transducin alpha subunit (TDalpha) GTPase is required. This reaction can be accelerated by GTPase-activating proteins (GAPs), e.g. PDEgamma. Recently we identified a second retinal GAP that interacts with TDalpha, RGS-r. Here we compare the GAP function of RGS-r and PDEgamma. Both proteins stimulated single turnover GTPase of TDalpha; however, RGS-r was more effective than PDEgamma. When added together, PDEgamma competitively inhibited the RGS-r-stimulated GTPase. In addition, the interaction of TDalpha in its GTP-bound form (TDalphaGTPgammaS), the transition state (TDalphaGDP*AMF) and the GDP-bound form (TDalphaGDP) with RGS-r and PDE, respectively, was measured by surface plasmon resonance. PDEgamma displayed highest affinity for TDalphaGTPgammaS, weaker affinity for TDalphaGDP*AMF, and weakest affinity for TDalphaGDP. RGS-r exhibited only a comparable high affinity for TDalphaGDP*AMF. We conclude that the observed competition between RGS-r and PDEgamma for TDalpha occurs when the hydrolysis of GTP is initiated. By competing with PDEgamma and removing it from TDalpha as well as increasing Pi release, RGS-r apparently facilitates signal termination and TDalpha recycling.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1997

Identification of G protein-coupled receptors potently stimulating migration of human transitional-cell carcinoma cells.

The expression of G protein-coupled receptors inducing calcium mobilization and stimulating cell migration was examined in human transitional-cell carcinoma (J82) cells. Measurements of cytoplasmic Ca2+ concentration ([Ca2+]i) and phospholipase C activity indicated that these cells express several calcium-mobilizing receptors, including those for lysophosphatidic acid (LPA), thrombin, bradykinin, bombesin and histamine, of which only the LPA response was sensitive (approximately 50%) to pertussis toxin (PTX). Migration of J82 cells was strongly stimulated by LPA and thrombin, by 5- to 20-fold, whereas bradykinin, bombesin and histamine were ineffective. Migration induced by either LPA or thrombin was inhibited by the actin cytoskeleton-disrupting agent, cytochalasin B, by the Rho protein-inactivating Clostridium difficile toxin B, by preventing [Ca2+]i transients with an intracellular calcium-chelating agent, and by the phorbol ester, phorbol 12-myristate 13-acetate, which also blocked the LPA- and thrombin-induced [Ca2+]i increases. On the other hand, ADP-ribosylation of Gi type G proteins by PTX abrogated the migratory response to LPA, without affecting the thrombin effect. Similarly, raising cAMP levels inhibited, by about 50%, the LPA- but not the thrombin-induced J82 cell migration. In conclusion, human transitional-cell carcinoma (J82) cells express various G protein-coupled, calcium-mobilizing receptors, out of which only those for LPA and thrombin stimulate cell migration, indicating that phospholipase C-derived second messengers per se are not sufficient for initiating this response. The complex signal transduction processes leading to LPA- and thrombin-stimulated motility of these human carcinoma cells apparently involve several common, essential factors, such as [Ca2+]i changes and Rho protein-regulated reorganization of the cytoskeleton, as well as some distinct components, most notably distinct subtypes of heterotrimeric G proteins and apparently also distinct cAMP-sensitive targets.

Calcium↗

PubMed1996

RGS-r, a retinal specific RGS protein, binds an intermediate conformation of transducin and enhances recycling.

G proteins regulate intracellular signaling by coupling a cycle of guanine nucleotide binding and hydrolysis to transient changes of cellular functions. The mechanisms that control the recycling of transducin, the "pacesetting" G protein that regulates mammalian phototransduction, are unclear. We show that a novel retinal specific RGS-motif protein specifically binds to an intermediate conformation involved in GTP hydrolysis by transducin and accelerates phosphate release and the recycling of transducin. This specific interaction further rationalizes the kinetics of the phototransduction cascade and provides a general hypothesis to explain the mechanism of interaction of RGS proteins with other G proteins.

Amino Acid Sequence↗

PubMed1996

Species- and tissue-dependent diversity of G-protein beta subunit phosphorylation: evidence for a cofactor.

We previously reported that, in the membranes of HL-60 cells during activation of G-proteins, a phosphate transfer reaction occurs which involves transient G-protein beta subunit (G beta) phosphorylation [Wieland, Nürnberg, Ulibarri, Kaldenberg-Stasch, Schultz and Jakobs (1993) J. Biol. Chem. 268, 18111-18118]. Here, the generality of this phenomenon is evaluated by studying membranes of various tissues obtained from different mammalian species. All membranes tested expressed at least G beta 1 and G beta 2 subunits. Cell membranes from bovine and porcine brain and liver, rat brain and human blood cells exhibited predominantly G beta 1 or both subtypes at roughly equal concentrations. In contrast, significantly more G beta 2 immunoreactivity was detected in membranes from human placenta. Bovine and porcine liver membranes exhibited weak, G beta-specific immunoreactive signals. Conversely, these membranes showed the highest levels of G beta phosphorylation after incubation with [gamma-32P]GTP or 35S-labelled guanosine 5'-[gamma-thio]triphosphate. Interestingly, G beta-specific phosphorylation of membranes from human erythrocytes and platelets was very weak. G beta phosphorylation was confirmed by immunoprecipitation with G beta-specific antibodies, and the target amino acid was identified as histidine. On SDS/PAGE, phosphorylated or thiophosphorylated G beta-proteins differed in their apparent molecular size from unmodified G beta-proteins. Moreover, phosphorylated G beta-proteins differed in a species-dependent fashion in their electrophoretic mobility. Solubilization of membrane proteins with detergent did not abolish G beta phosphorylation. In contrast, reconstituted purified Gi/Go proteins showed no G beta phosphorylation. From these experiments we conclude that: (i) G beta phosphorylation represents a general phenomenon occurring in the cells of various species to different degrees, (ii) phosphorylated G beta-proteins exhibit species-dependent diverse electrophoretic mobilities, and (iii) G beta phosphorylation requires a membrane-associated cofactor(s) which is lost during routine G-protein purification.

Animals↗

PubMed1996

Cytoskeletal inhibitors impair Ca2+ elevations via neuropeptide Y and other Gi-coupled receptors.

Neuropeptide Y, alpha 2-adrenoceptors, thrombin and certain muscarinic acetylcholine receptors can couple to elevations of intracellular free Ca2+ concentrations via Gi-proteins. We have studied the effects of inhibitors of microtubules (colchicine, nocodazole, vinblastine) and microfilaments (cytochalasin B, cytochalasin D) on these effects in human erythroleukemia (HEL) cells. Both types of inhibitors reduced neuropeptide Y-, adrenaline- (via alpha 2A-adrenoceptors) and thrombin-stimulated Ca2+ elevations while the inactive analog beta-lumicolchicine was without inhibitory effects. Similarly, in SK-N-MC cells vinblastine inhibited neuropeptide Y and carbachol (via muscarinic receptors) stimulated Ca2+ elevations. In HEL cells the inhibitory effects of the microfilament inhibitor cytochalasin D and the microtubule inhibitor colchicine were not additive. Colchicine, nocodazole or cytochalasin D did not affect the binding of the agonist neuropeptide Y. On the other hand, neuropeptide Y and thrombin significantly stimulated GTP gamma S binding in the absence but not in the presence of colchicine, vinblastine or cytochalasin B. This was not due to sequestration of G-protein alpha-subunits, since nocodazole did not affect the distribution of immunodetectable Gi alpha 1/2 or Gi alpha 3 between membrane and cytosolic fractions. We conclude that disruption of microfilaments or microtubules impairs Ca2+ elevations by neuropeptide Y and other Gi-coupled receptors by inhibiting receptor/Gi-protein interaction; this does not involve impairment of agonist binding to the receptor or redistribution of Gi-protein alpha-subunits.

Animals↗

PubMed1996

Receptor-induced translocation of activated guanine-nucleotide-binding protein alpha i subunits to the cytoskeleton in myeloid differentiated human leukemia (HL-60) cells.

The regulation of the cytoskeletal localization of guanine-nucleotide-binding protein alpha i subunits by formyl peptide receptors was studied in myeloid differentiated human leukemia (HL-60) cells. Stimulation of formyl peptide receptors with N-formyl-Met-Leu-Phe (fMet-Leu-Phe) transiently increased the amount of alpha i subunits in the Triton X-100-insoluble cytoskeleton. Similar to the biphasic regulation of the actin content, fMet-Leu-Phe ( > or = 10 nM) rapidly increased the cytoskeletal alpha i content (about threefold at 30 s), which was followed by a rapid reversal to control levels. The formyl peptide receptor increased the cytoskeletal content of both alpha i subtypes, alpha i2 and alpha i3- present in HL-60 cells. In cells permeabilized with Staphylococcus aureus alpha-toxin, fMet-Leu-Phe increased binding of the stable GTP analogue, guanosine 5'-[gamma-thio]triphosphate (GTP[S]), to cytoskeletal proteins in a pertussis-toxin-sensitive manner, which was completely abolished by the F-actin-disrupting agent, cytochalasin B. Using the photoreactive GTP analogue, m-acetylanilido-GTP, the formyl peptide receptor-regulated GTP binding sites at the cytoskeleton were identified as 40-kDa proteins, the molecular size of alpha i subunits. Cytoskeleton prepared from stimulated cells did not exhibit increased GTP[S] binding, which suggests that activated alpha i subunits are translocated to the cytoskeleton. Finally, in alpha-toxin-permeabilized HL-60 cells, fMet-Leu-Phe and GTP[S] cooperatively stimulated actin polymerization. In conclusion, evidence is provided that chemoattractant receptors cause translocation of activated alpha i subunits to the cytoskeleton coincidentally with F-actin formation. The data therefore argue for a potential role of translocated alpha i subunits in the process of receptor-induced actin polymerization.

Bacterial Toxins↗