The signal transduction system of the leukotriene D4 receptor

Crooke, Stanley T.; Mattern, Mike; Sarau, Henry M.; Winkler, James D.; Balcarek, J M; Wong, Angela; Bennett, C. Frank

doi:10.1016/0165-6147(89)90206-x

Cited by 87 publications

(33 citation statements)

References 18 publications

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“…This interpretation of our findings is in accordance with the well-established concept that seven-transmembrane receptors can activate several different types of heterotrimeric G-proteins (7,10,11). Moreover, in differentiated human U937 cells, the LTD 4 -induced Ca 2ϩ response is only partially blocked by pertussis toxin, suggesting that this receptor is coupled to pertussis toxin-sensitive as well as insensitive G-proteins (11). The identity of the indicated type of LTD 4 -activated pertussis toxin-insensitive G-protein(s) remains to be discovered.…”

Section: Discussionsupporting

confidence: 81%

“…This assumption is based on the following observations: activation of the G i3 -protein is sensitive to pertussis toxin; pertussis toxin impairs the interaction between such G-proteins and seven-transmembrane receptors; and LTD 4 -induced mobilization of calcium is insensitive to pertussis toxin (10). This interpretation of our findings is in accordance with the well-established concept that seven-transmembrane receptors can activate several different types of heterotrimeric G-proteins (7,10,11). Moreover, in differentiated human U937 cells, the LTD 4 -induced Ca 2ϩ response is only partially blocked by pertussis toxin, suggesting that this receptor is coupled to pertussis toxin-sensitive as well as insensitive G-proteins (11).…”

Section: Discussionsupporting

confidence: 79%

“…The LTD 4 receptor was also recently cloned and shown to belong to the seven-transmembrane group (7,8), which is in accordance with previous observations reported from our laboratory (10) and by other investigators (9) showing that LTD 4 signaling occurs through heterotrimeric G-proteins. We have also demonstrated (10), as have others (11), that the cytosolic free Ca 2ϩ concentration is increased in cells stimulated with LTD 4 . Furthermore, we have concluded that the LTD 4 -induced mobilization of Ca 2ϩ involves PLC-␥1 in the human intestinal epithelial cell line Int 407 (12).…”

supporting

confidence: 55%

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Leukotriene D4 Triggers an Association between Gβγ Subunits and Phospholipase C-γ1 in Intestinal Epithelial Cells

Thodeti¹,

Adolfsson

Juhas

et al. 2000

Journal of Biological Chemistry

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The proinflammatory mediator leukotriene D 4 (LTD 4 ) binds to the seven-transmembrane receptor CYSLT 1 . Although this leukotriene plays an important biological role, its intracellular signaling pathways are only partly known. In previous experiments, we found that LTD 4 induced tyrosine phosphorylation and translocation of phospholipase (PLC)-␥1 to a plasma membrane fraction in a human epithelial cell line (Int 407). In the present study, we further examined these signaling events and found that LTD 4 induced a rapid interaction between G␤␥ subunits and PLC-␥1; results obtained with GST fusion proteins of PLC-␥1 suggest that this interaction is mediated via the pleckstrin homology domain of PLC-␥1. Moreover, LTD 4 induced an increased association of c-Src with PLC-␥1, and the selective Src family tyrosine kinase inhibitor PP1 blocked both LTD 4 -induced tyrosine phosphorylation of PLC-␥1 and the association of PLC-␥1 with G␤␥ subunits. The relevance of these observations in intracellular calcium signaling was investigated by microinjecting cells with anti-G␤, anti-PLC-␥1, or anti-c-Src antibodies and by pretreatment with PP1. LTD 4 -induced calcium mobilization was blocked by each of the indicated antibodies (but not isotypematched control antibodies) and by PP1. Our data suggest that G␤␥ subunits can, directly or indirectly, serve as membrane-bound partners for PLC-␥1 and c-Src and that each of these proteins is essential for LTD 4 -induced downstream PLC-␥1 signaling. Leukotrienes (LTs)1 are metabolites of the fatty acid arachidonate, produced by the activation of 5-lipoxygenase, and are powerful inflammatory mediators (1). LTs are extremely potent and exert a large number of functional effects; for example, they increase vascular permeability and cause contraction of smooth muscle cells, trachea, parenchyma, and ileum (2, 3).It is generally assumed that LT-induced effects are mediated via specific plasma membrane receptors. Yokomizo et al. (4) have cloned and sequenced the LTB 4 receptor from a cDNA library of a gene that encodes an orphan seven-spanning receptor on human B-lymphoblasts (5). In studying Chinese hamster ovary LTB 4 receptor cells, Yokomizo et al. (4) also noted that the LTB 4 receptor, which belongs to the seven-transmembrane-spanning receptor group, can bind to two different Gproteins, one that is sensitive and one that is insensitive to pertussis toxin. The former G-protein has been identified as ␣ i and the latter as ␣ 16 , and both appear to signal via phospholipase C-␤ (PLC-␤) in COS-7 cells (6). The LTD 4 receptor was also recently cloned and shown to belong to the seven-transmembrane group (7,8), which is in accordance with previous observations reported from our laboratory (10) and by other investigators (9) showing that LTD 4 signaling occurs through heterotrimeric G-proteins. We have also demonstrated (10), as have others (11), that the cytosolic free Ca 2ϩ concentration is increased in cells stimulated with LTD 4 . Furthermore, we have concluded that the LTD 4 -induced mobiliza...

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 79%

supporting

confidence: 55%

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Leukotriene D4 Triggers an Association between Gβγ Subunits and Phospholipase C-γ1 in Intestinal Epithelial Cells

Thodeti¹,

Adolfsson

Juhas

et al. 2000

Journal of Biological Chemistry

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“…When the BMMC pretreated with 0.1 mM EDTA in Ca 21 -free Tyrode's solution was stimulated with antigen, rapid [Ca 2+]i elevation, the degree and duration of which were similar to those seen in the BMMC treated without EDTA, was observed (Fig. 7D) (43), are supposed to be mostly released when the second Ca 21 influx increases. Irrespective of which Ca channel is opened for the first or second Ca2+ influx, the Ca channel inducing the second phase of Ca 21 influx must be differ ent from that inducing the first phase.…”

Section: Resultsmentioning

confidence: 83%

Two-Phase Increment of Ca2+ Uptake, Intracellular Ca2+ Concentration, and Histamine Release Following Antigen Stimulation in Mouse Bone Marrow-Derived Mast Cells (BMMC)

Yamamura

Masuda

Ohkawa

et al. 1994

Japanese Journal of Pharmacology

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ABSTRACT-The relationship between the influx of Ca" into cells or cytosolic Ca" concentration ([Ca 211i) and the histamine release following antigen stimulation in mouse bone marrow-derived mast cells (BMMC) was examined, and the results were compared with those from human lung mast cells (HLMC) and rat peritoneal mast cells (RPMC) in some experiments. Anaphylactic histamine release from BMMC as well as HLMC, but not that from RPMC, was dependent on the extracellular Ca2+. When BMMC were challenged by antigen following radioactive "Ca 2+ addition, two phases of "Ca 21 influx into the cells were observed. The first phase, which was initiated and completed within 30 sec and 2 min, respectively, after antigen treat ment, appeared to be related to anaphylactic histamine release. The second influx began 30 sec subsequent to the first one and lasted for at least 2 min, and this occurred after the completion of the histamine release; So far, it is not known how this second influx participates in the intracellular event(s). On the other hand, only one sustained elevation of [Ca 2+]; occurred that reached its maximum within 2 min after antigen stimulation. Following stimulation of BMMC with antigen in the absence of Ca", Ca 2' addition 1 to 5 min later time-dependently enhanced the histamine release, although the release was deteriorated by further ex tension of Ca" addition. In contrast, the releasability of HLMC was rapidly decreased. These results in dicate that extracellular Ca 2+ not only is prerequisite for anaphylactic histamine release from BMMC, but also may modulate the release and participate in some intracellular event(s) which has yet to be focused upon.

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“…LTC4, LTD4, LTE, and its metabolites [ S , 61. Leukotrienes exert their biological effects through distinct receptors at the cell membrane [12]. The cysteinyl leukotriencs are rapidly eliminated from the blood circulation [9, 1 I] by a temperature-and ATP-dependent uptake system at the sinusoidal membrane of hepatocytes 113 -151.…”

mentioning

confidence: 99%

Direct photoaffinity labeling of leukotriene binding sites

Falk

Müller

Huber

et al. 1989

European Journal of Biochemistry

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Due to their conjugated double bonds the leukotrienes themselves are photolabile compounds and may therefore be used directly for photoaffinity labcling of leukotriene binding sites. Cryofixation eliminates unspecific labeling taking place in solution by photoisomcrs and photodegradation products of leukotrienes. After fixation of receptor ligand interactions by shock-freezing of the samples, irradiation-induced highly reactive excited states andlor intermediates can form covalent bonds with the respective binding sitc in the frozen state.After cryofixation of a solution of albumin incubated with [3H8]leukotriene E4, irradiation at 300 nm resulted in time-dcpendent incorporation of radioactivity into the protein. Photoaffinity labeling of rat as well as of human blood serum with [3H8]leukotriene E4 after cryofixation rcvcaled that only one polypeptide with an M , of 67000 was labeled. This polypeptide was identified as albumin.Photoaffinity labeling of rat liver membrane subfractions enriched with sinusoidal membranes resulted in the labeling of a polypeptide with an apparent M , of 48 000, whereas no polypeptide was predominantly labeled in the subfraction enriched with canalicular membranes. Photoaffinity labeling of isolated hepatocytes disclosed different leukotriene E4 binding polypeptides. In the particulate fraction of hcpatocytes a polypeptide with an apparent M , of 48 000 was labeled predominantly, whereas in the soluble fraction several polypeptides were labeled to a similar extent. One of these, with an apparent M , of 25000, was identified as subunit 1 of glutathione transfcrases by immunoprecipitation.The method of direct photoaffinity labeling in the frozen state after cryofixation using leukotrienes as photoactivatable compounds, as exemplified by leukotriene E4, may be most useful for the identification and characterization of various leukotriene binding sites, including receptors, leukotriene-metabolizing enzymes, and transport systems.Leukotrienes arc proinflammatory mediators active in vivo at nanoniolar concentrations [I -1 I]. They comprise the chemotactic leukotriene B4 (LTB,) as well as the cysteinyl leukotrienes. LTC4, LTD4, LTE, and its metabolites [ S , 61. Leukotrienes exert their biological effects through distinct receptors at the cell membrane [12]. The cysteinyl leukotriencs are rapidly eliminated from the blood circulation [9, 1 I] by a temperature-and ATP-dependent uptake system at the sinusoidal membrane of hepatocytes 113 -151. Moreover, cysteinyl leukotriene uptake has been demonstrated in renal cells and in intestinal mucosal cells [13], whereas AS-30D rat hepatoma cell% are complctely deficient in the uptake of these lipid mediators [I 51. Hepatocellular uptake is followed by partial intracellular metabolism and by excretion of cysteinyl leukotrienes and their degradation products into bile [9, 1 1,

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The signal transduction system of the leukotriene D4 receptor

Cited by 87 publications

References 18 publications

Leukotriene D4 Triggers an Association between Gβγ Subunits and Phospholipase C-γ1 in Intestinal Epithelial Cells

Leukotriene D4 Triggers an Association between Gβγ Subunits and Phospholipase C-γ1 in Intestinal Epithelial Cells

Two-Phase Increment of Ca2+ Uptake, Intracellular Ca2+ Concentration, and Histamine Release Following Antigen Stimulation in Mouse Bone Marrow-Derived Mast Cells (BMMC)

Direct photoaffinity labeling of leukotriene binding sites

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