FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1567382319> ?p ?o ?g. }

• W1567382319 endingPage "2508" @default.
• W1567382319 startingPage "2505" @default.
• W1567382319 abstract "Jun kinases (JNK) are involved in the stress response of mammalian cells. Stimulation of JNK can be induced by stress factors and by agonists of tyrosine kinase and G protein-coupled receptors. G protein-dependent receptors stimulate JNK via Gβγ subunits of heterotrimeric G proteins, but the subsequent signaling reaction has been undefined. Here we demonstrate JNK activation in COS-7 cells by Gβγ-stimulated phosphoinositide 3-kinase γ (PI3Kγ). Signal transduction from PI3Kγ to JNK can be suppressed by dominant negative mutants of Ras, Rac, and the protein kinase PAK. These results identify PI3Kγ as a mediator of Gβγ-dependent regulation of JNK activity. Jun kinases (JNK) are involved in the stress response of mammalian cells. Stimulation of JNK can be induced by stress factors and by agonists of tyrosine kinase and G protein-coupled receptors. G protein-dependent receptors stimulate JNK via Gβγ subunits of heterotrimeric G proteins, but the subsequent signaling reaction has been undefined. Here we demonstrate JNK activation in COS-7 cells by Gβγ-stimulated phosphoinositide 3-kinase γ (PI3Kγ). Signal transduction from PI3Kγ to JNK can be suppressed by dominant negative mutants of Ras, Rac, and the protein kinase PAK. These results identify PI3Kγ as a mediator of Gβγ-dependent regulation of JNK activity. Interaction of cells with a wide variety of agonists results in a stimulation of intracellular mitogen-activated protein kinase (MAPK) 1The abbreviations used are: MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide 3-kinase; ERK, extracellular signal-regulated kinase; JNK (or SAPK), c-Jun NH2-terminal kinase (or stress-activated protein kinase); PIP3, phosphatidylinositol 3,4,5-trisphosphate; HA, hemagglutinin; MOPS, 4-morpholinepropanesulfonic acid. 1The abbreviations used are: MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide 3-kinase; ERK, extracellular signal-regulated kinase; JNK (or SAPK), c-Jun NH2-terminal kinase (or stress-activated protein kinase); PIP3, phosphatidylinositol 3,4,5-trisphosphate; HA, hemagglutinin; MOPS, 4-morpholinepropanesulfonic acid. cascades. MAPKs control the expression of genes that are important for the regulation of many cell functions including proliferation and differentiation. In mammalian cells three parallel MAPK pathways have been characterized so far (1Cano E. Mahadevan L.C. Trends Biochem. Sci. 1995; 20: 117-122Abstract Full Text PDF PubMed Scopus (995) Google Scholar). The canonical MAPK cascade composed of Raf, MEK, and ERK is regulated by the Ras GTPase in response to agonists of tyrosine kinase and G protein-coupled receptors. ERK species catalyze the phosphorylation of transcription factors including Elk-1, thus controlling the expression of several genes (2Davis R.J. J. Biol. Chem. 1993; 270: 14553-14556Google Scholar). A second MAPK cascade that is stimulated by osmotic stress regulates the activity of the protein kinase p38. Signal transduction to p38 and the function of this pathway are still unclear. Like p38 the elements of the Jun kinase (JNK) cascade as a third MAPK pathway are involved in the stress response of mammalian cells. JNK can be stimulated by stress factors like interleukin 1 and tumor necrosis factor but also by agonists of tyrosine kinase and G protein-coupled receptors (3Kyriakis J. Banerjee P. Nikolakaki E. Dai T. Rubie E. Ahmad M. Avruch J. Woodgett J. Nature. 1994; 369: 156-160Crossref PubMed Scopus (2402) Google Scholar, 4Coso O.A. Chiariello M. Kalinec G. Kyriakis J.M. Woodgett J. Gutkind J.S. J. Biol. Chem. 1995; 270: 5620-5624Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar). Available evidences point to an involvement of the small GTPase Rac and several protein kinases in the regulation of JNK activity (5Ridley A.J. Curr. Biol. 1996; 6: 1256-1264Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar). In some cellular systems the STE 20 homologue PAK was found to act as a JNK kinase kinase kinase (6Bagrodia S. Derijard B. Davis R.J. Cerione R.A. J. Biol. Chem. 1995; 270: 27995-27998Abstract Full Text Full Text PDF PubMed Scopus (597) Google Scholar). PAK is able to activate JNK via sequential stimulation of the protein kinases MEKK and SEK. The mechanism of signal transduction from G protein-coupled receptors to the JNK cascade is only partially understood. Using COS-7 cells as a transient expression system a recent report showed the involvement of Gβγ subunits of heterotrimeric G proteins in the stimulation of JNK by agonists of the G protein-coupled muscarinergic receptor m2 (7Coso O.A. Teramoto H. Simonds W.F. Gutkind J.S. J. Biol. Chem. 1996; 271: 3963-3966Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar). Additionally the small GTPases Ras and Rac have been demonstrated to mediate signal transduction from G protein-coupled receptor to JNK, but the topology of the signaling path from Gβγ to Ras and Rac remains unknown (7Coso O.A. Teramoto H. Simonds W.F. Gutkind J.S. J. Biol. Chem. 1996; 271: 3963-3966Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar, 8Minden A. Lin A. Claret F.-X. Abo A. Karin M. Cell. 1995; 81: 1147-1157Abstract Full Text PDF PubMed Scopus (1440) Google Scholar, 9Coso O.A. Chiariello M. Yu J.-C. Crespo P. Xu N. Miki T. Gutkind J.S. Cell. 1995; 81: 1137-1146Abstract Full Text PDF PubMed Scopus (1552) Google Scholar). One candidate for the link of G protein-coupled receptor and JNK cascade is phosphoinositide 3-kinase γ (PI3Kγ). This subspecies of the PI3K family is stimulated in vitro by Gβγ and recently has been shown to be involved in signal transduction from G protein-coupled receptor to the ERK path of MAPK cascades (10Lopez-Ilasaca M. Crespo P. Pellici P.G. Gutkind S. Wetzker R. Science. 1997; 275: 394-397Crossref PubMed Scopus (627) Google Scholar). We now present evidences that JNK stimulation by an agonist of the m2 muscarinergic receptor and by Gβγ also implies a PI3K. Overexpression of PI3Kγ in COS-7 cells induces a significant increase of JNK activity. Stimulation of JNK by Gβγ can be suppressed by the PI3K inhibitor wortmannin and a lipid kinase negative mutant of PI3K. Dominant negative mutants of Ras, Rac, and PAK significantly reduce the stimulatory effect of PI3Kγ on JNK. Thus PI3Kγ seems to act as an intermediate connecting G protein-coupled receptors to the JNK cascade. COS-7 cells (ATCC) were cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. Cells were split the day before transfection. Subconfluent cells were transfected with pcDNAIII-HA-JNK or pcDNAIII-HA-MAPK and additional DNAs, following the DEAE-dextran technique, adjusting the total amount of DNA to 5 μg per plate with vector DNA when necessary. Assays were performed 48 h after transfection (9Coso O.A. Chiariello M. Yu J.-C. Crespo P. Xu N. Miki T. Gutkind J.S. Cell. 1995; 81: 1137-1146Abstract Full Text PDF PubMed Scopus (1552) Google Scholar). For JNK assays the cells were serum-starved for 2 h, whereas for MAPK the cells were starved overnight in serum-free medium. Expression plasmids for an epitope-tagged JNK and MAPK, pcDNA3 HA-JNK and pcDNA3 MAPK, respectively, as well as expression plasmids for the dominant negative mutants of the small GTP-binding proteins Ras, RhoA, Rac1, and Cdc42 have been described (9Coso O.A. Chiariello M. Yu J.-C. Crespo P. Xu N. Miki T. Gutkind J.S. Cell. 1995; 81: 1137-1146Abstract Full Text PDF PubMed Scopus (1552) Google Scholar, 11Crespo P. Xu N. Simonds W.F. Gutkind J.S. Nature. 1994; 369: 418-420Crossref PubMed Scopus (756) Google Scholar). PI3Kγ and dominant negative PI3Kγ were used as described previously (10Lopez-Ilasaca M. Crespo P. Pellici P.G. Gutkind S. Wetzker R. Science. 1997; 275: 394-397Crossref PubMed Scopus (627) Google Scholar). pcDNA3-p101 was kindly provided by Dr. Len Stephens and prepared as published recently (12Stephens L.R. Eguinoa A. Erdjument-Bromage H. Lui M. Cooke F. Coadwell J. Smrcka A.S. Thelen M. Cadwallader K. Tempst P. Hawkins P.T. Cell. 1997; 89: 105-114Abstract Full Text Full Text PDF PubMed Scopus (490) Google Scholar). An expression plasmid for the N-terminal 150-amino acid noncatalytic domain of Pak1, which contains the Rac/Cdc42 binding region, was cloned into pcDNA3 vector coding the NH2-terminal myristoylation membrane localization signal from c-Src (13Takeya T. Hanafusa H. Cell. 1983; 32: 881-889Abstract Full Text PDF PubMed Scopus (297) Google Scholar, 14Teramoto H. Crespo P. Coso O.A. Igishi T. Xu N. Gutkind J.S. J. Biol. Chem. 1996; 271: 25731-25734Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar). The final construct was designated pcDNA3-myr-PAK(N). Efficacy of dominant negative mutants of PI3Kγ, Ras, RhoA, Rac1, Cdc42, and PAK to suppress muscarinergic response in COS-7 cells has been established recently (7Coso O.A. Teramoto H. Simonds W.F. Gutkind J.S. J. Biol. Chem. 1996; 271: 3963-3966Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar, 10Lopez-Ilasaca M. Crespo P. Pellici P.G. Gutkind S. Wetzker R. Science. 1997; 275: 394-397Crossref PubMed Scopus (627) Google Scholar, 14Teramoto H. Crespo P. Coso O.A. Igishi T. Xu N. Gutkind J.S. J. Biol. Chem. 1996; 271: 25731-25734Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar). JNK assays in cells transfected with an epitope-tagged JNK construct (HA-JNK) was determined as described previously (9Coso O.A. Chiariello M. Yu J.-C. Crespo P. Xu N. Miki T. Gutkind J.S. Cell. 1995; 81: 1137-1146Abstract Full Text PDF PubMed Scopus (1552) Google Scholar) using purified, bacterially expressed GST-ATF2(96) fusion protein as a substrate. Briefly, serum-starved cells left untreated or stimulated with various agents were lysed, and after centrifugation, clarified supernatants were immunoprecipitated with an anti-hemagglutinin monoclonal antibody 12CA5 (Babco, Richmond, CA) for 1–2 h at 4 °C, and immunocomplexes were recovered with the aid of GammaBind (Pharmacia, Uppsala). Pellets were then washed three times with phosphate-buffered saline solution, supplemented with 1% Nonidet P-40, and 2 mm sodium vanadate, once with 0.5 mLiCl in 100 mm Tris, pH 7.5, and once with kinase reaction buffer (12.5 mm MOPS, pH 7.5, 12.5 mmβ-glycerophosphate, 7.5 mm MgCl2, 0.5 mm EGTA, 0.5 mm sodium fluoride, 0.5 mm vanadate). Reactions were performed in a 30-μl volume of kinase reaction buffer containing 1 μCi of [γ-32P]ATP/reaction, 20 μm unlabeled ATP, and 1.5 mg/ml substrate at 30 °C for 30 min. Reactions were terminated by addition of 5× Laemmli buffer, boiled, and electrophoresed in 12% polyacrylamide gel. Phosphorylated GST-ATF2(96) was visualized by autoradiography and quantified with a PhosphorImager. MAPK activity in cells transfected with an epitope-tagged MAPK (HA-MAPK) was determined as described previously (11Crespo P. Xu N. Simonds W.F. Gutkind J.S. Nature. 1994; 369: 418-420Crossref PubMed Scopus (756) Google Scholar). In each case, parallel samples were immunoprecipitated with anti-HA antibody and processed by Western blot analysis using the appropriate antibody (Santa Cruz Technology, Santa Cruz, CA). Immunocomplexes were visualized by enhanced chemiluminescence detection (Amersham) with the use of goat antiserum to rabbit or mouse immunoglobulin G coupled to horseradish peroxidase (Santa Cruz Technology). To investigate signaling from G protein-coupled receptor to JNK the muscarinergic m2 receptor has been transiently expressed in COS-7 cells. Confirming previous results (7Coso O.A. Teramoto H. Simonds W.F. Gutkind J.S. J. Biol. Chem. 1996; 271: 3963-3966Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar) we observed an increase of JNK activity after treatment with the receptor agonist carbachol (Fig. 1 A). Overexpression of Gβγ mimics the effect of carbachol on JNK. As shown in Fig. 1 Aboth m2- and Gβγ-mediated stimulation could be effectively suppressed by wortmannin, a specific inhibitor of PI3K. In contrast JNK activation by the stress-inducing agent anisomycin was unaffected by wortmannin, demonstrating the specificity of this approach. Another PI3K inhibitor LY 294002 decreased JNK stimulation induced by Gβγ in a dose-dependent manner (Fig. 1 B). Together these data point to an involvement of PI3K in the stimulation of JNK by G protein-coupled receptor. Trying to outline the PI3K species that induces Gβγ-dependent JNK activation we expressed PI3Kγ in COS-7 cells. As shown in Fig. 2 A, PI3Kγ moderately stimulated JNK activity. This effect could be significantly enhanced by coexpression of p101, a PI3Kγ-binding protein recently discovered (12Stephens L.R. Eguinoa A. Erdjument-Bromage H. Lui M. Cooke F. Coadwell J. Smrcka A.S. Thelen M. Cadwallader K. Tempst P. Hawkins P.T. Cell. 1997; 89: 105-114Abstract Full Text Full Text PDF PubMed Scopus (490) Google Scholar). p101 alone was unable to induce JNK stimulation. For a comparison Fig. 2 A expresses the individual effects of p101, PI3Kγ, and PI3Kγ + p101 on MAP kinase (ERK) activity. Interestingly p101 exhibited significantly lower potency to affect PI3Kγ-dependent MAPK activity than JNK induced by PI3Kγ. To examine possible autocrine reactions of the transfectants we analyzed the effects of conditioned media from COS-7 cells expressing PI3Kγ and/or p101 on naive cells. Supernatants of the transfected cells did not induce any measurable stimulation of JNK activity in untreated cells, thus providing evidence for direct signaling from PI3Kγ and p101 to JNK (data not shown). Fig. 2 B demonstrates the dependence of JNK activation on the expression levels of p101 and PI3Kγ. Thus optimal stimulation of JNK seems to depend on PI3Kγ and p101. The activatory effect of PI3Kγ on JNK could be completely inhibited by wortmannin suggesting an important role of the kinase activities of the PI3K (Fig. 3 A). PI3Kγ recently has been shown to exhibit a significant ability to catalyze autophosphorylation in addition to its lipid kinase activity (15Stoyanova S. Bulgarelli-Leva G. Kirsch C. Hanck T. Klinger R. Wetzker R. Wymann M.P. Biochem. J. 1997; 324: 489-495Crossref PubMed Scopus (100) Google Scholar). Both kinase activities depend on magnesium and can be inhibited by nanomolar concentrations of wortmannin. A recently described mutant of PI3Kγ K799R, which does not express significant lipid kinase and protein kinase activities, was able to suppress the JNK stimulation induced by Gβγ (Fig. 3 B). Together with our previous report (10Lopez-Ilasaca M. Crespo P. Pellici P.G. Gutkind S. Wetzker R. Science. 1997; 275: 394-397Crossref PubMed Scopus (627) Google Scholar) these findings provide clear evidence that PI3Kγ links both JNK and MAPK to G protein-coupled receptors. Involvement of PI3Kα, which recently has been shown to mediate signaling of platelet-derived growth factor receptor tyrosine kinase to JNK (16Lopez-Ilasaca M. Li W. Uren A. Yu J. Kazlauskas A. Gutkind J.S. Heidaran M.A. Biochem. Biophys. Res. Commun. 1997; 232: 273-277Crossref PubMed Scopus (58) Google Scholar) seems improbable. The recently described involvement of Ras and Rac in signal transduction from G protein-coupled receptors to JNK prompted us to investigate a possible role of these small GTPases in JNK stimulation induced by PI3Kγ. As shown in Fig. 4 A coexpression of dominant negative forms of Ras and Rac prevented activation of JNK by PI3Kγ. In contrast coexpression of the negative mutants of two other small GTPases RhoA and Cdc42 did not affect the stimulation of JNK by PI3Kγ. Therefore Ras and Rac1 seem to represent essential elements of the signaling path from PI3Kγ to JNK. Expression of βARK as a binding protein for Gβγ (9Coso O.A. Chiariello M. Yu J.-C. Crespo P. Xu N. Miki T. Gutkind J.S. Cell. 1995; 81: 1137-1146Abstract Full Text PDF PubMed Scopus (1552) Google Scholar, 10Lopez-Ilasaca M. Crespo P. Pellici P.G. Gutkind S. Wetzker R. Science. 1997; 275: 394-397Crossref PubMed Scopus (627) Google Scholar) also suppressed JNK stimulation induced by PI3Kγ (data not shown). This effect points to an essential role of Gβγ as a link of G protein-coupled receptors to PI3Kγ. We next explored a possible involvement of protein kinase PAK in downstream signaling from PI3Kγ to JNK. The coexpression of a dominant negative mutant of this protein kinase also induced a partial suppression of JNK stimulation by Gβγ, PI3Kγ, and a constitutively active mutant of Rac (Fig. 4 B). Thus signaling from G protein-coupled receptor to JNK appears to require Gβγ, PI3Kγ, Ras, Rac, and PAK. Nevertheless the sequence of events connecting PI3Kγ and JNK remains unclear. A PI3Kγ effect on Ras has been proposed in our previous report on ERK activation by PI3Kγ (10Lopez-Ilasaca M. Crespo P. Pellici P.G. Gutkind S. Wetzker R. Science. 1997; 275: 394-397Crossref PubMed Scopus (627) Google Scholar). In this paper we provide evidences that Ras could be activated by PI3Kγ via a Src-type tyrosine kinase, the adapter proteins Shc and Grb2, and the guanine nucleotide exchange factor Sos. Stimulated in this way Ras could act as a dissociation point for signals from PI3Kγ to ERK and JNK. Such a bifurcating function of Ras as a regulator of the Raf-ERK path and signal transduction to Rac, PAK, and JNK has been proposed (6Bagrodia S. Derijard B. Davis R.J. Cerione R.A. J. Biol. Chem. 1995; 270: 27995-27998Abstract Full Text Full Text PDF PubMed Scopus (597) Google Scholar). Despite the attractiveness of this model some experimental data point to a more complex relation of the signaling proteins involved. Thus the differential effects of p101 on the PI3Kγ-dependent stimulation of ERK and JNK cannot be explained by simple sequential signal transduction from PI3Kγ via the lipid kinase product PIP3 to Ras and subsequent stimulation of JNK and ERK paths. One possible explanation for the distinct effects of PI3Kγ and its ligands on the MAPK cascades could be the involvement of signaling activities of the enzyme in addition to PIP3 production. Wortmannin-sensitive protein kinase activity of PI3Kγ has been reported (15Stoyanova S. Bulgarelli-Leva G. Kirsch C. Hanck T. Klinger R. Wetzker R. Wymann M.P. Biochem. J. 1997; 324: 489-495Crossref PubMed Scopus (100) Google Scholar). If Gβγ and p101 produce divergent effects on the lipid kinase and protein kinase activities of PI3Kγ and if both activities are important for signal transduction different downstream events could be expected. The individual signaling functions of PI3Kγ lipid kinase and protein kinase activities are currently under investigation. The effects of PI3Kγ on different MAPK cascades clearly represent another example for the complex interrelations of these intracellular signaling proteins. We are very grateful to Drs. Len Stephens and Phill Hawkins for providing us with the pcDNA3-p101 construct." @default.
• W1567382319 created "2016-06-24" @default.
• W1567382319 creator A5038753309 @default.
• W1567382319 creator A5048579901 @default.
• W1567382319 creator A5069223693 @default.
• W1567382319 date "1998-01-01" @default.
• W1567382319 modified "2023-10-13" @default.
• W1567382319 title "Phosphoinositide 3-Kinase γ Is a Mediator of Gβγ-dependent Jun Kinase Activation" @default.
• W1567382319 cites W1555692789 @default.
• W1567382319 cites W1567065545 @default.
• W1567382319 cites W1573821584 @default.
• W1567382319 cites W1755015038 @default.
• W1567382319 cites W2026326077 @default.
• W1567382319 cites W2026951979 @default.
• W1567382319 cites W2039610291 @default.
• W1567382319 cites W2041609971 @default.
• W1567382319 cites W2042584344 @default.
• W1567382319 cites W2044835236 @default.
• W1567382319 cites W2047605827 @default.
• W1567382319 cites W2055181868 @default.
• W1567382319 cites W2073541193 @default.
• W1567382319 cites W2090891207 @default.
• W1567382319 cites W2092014913 @default.
• W1567382319 cites W2093115609 @default.
• W1567382319 doi "https://doi.org/10.1074/jbc.273.5.2505" @default.
• W1567382319 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9446550" @default.
• W1567382319 hasPublicationYear "1998" @default.
• W1567382319 type Work @default.
• W1567382319 sameAs 1567382319 @default.
• W1567382319 citedByCount "90" @default.
• W1567382319 countsByYear W15673823192012 @default.
• W1567382319 countsByYear W15673823192014 @default.
• W1567382319 countsByYear W15673823192015 @default.
• W1567382319 countsByYear W15673823192019 @default.
• W1567382319 countsByYear W15673823192020 @default.
• W1567382319 crossrefType "journal-article" @default.
• W1567382319 hasAuthorship W1567382319A5038753309 @default.
• W1567382319 hasAuthorship W1567382319A5048579901 @default.
• W1567382319 hasAuthorship W1567382319A5069223693 @default.
• W1567382319 hasBestOaLocation W15673823191 @default.
• W1567382319 hasConcept C137361374 @default.
• W1567382319 hasConcept C184235292 @default.
• W1567382319 hasConcept C185592680 @default.
• W1567382319 hasConcept C2107291 @default.
• W1567382319 hasConcept C2781322055 @default.
• W1567382319 hasConcept C62478195 @default.
• W1567382319 hasConcept C75217442 @default.
• W1567382319 hasConcept C86803240 @default.
• W1567382319 hasConcept C90934575 @default.
• W1567382319 hasConcept C95444343 @default.
• W1567382319 hasConcept C97029542 @default.
• W1567382319 hasConceptScore W1567382319C137361374 @default.
• W1567382319 hasConceptScore W1567382319C184235292 @default.
• W1567382319 hasConceptScore W1567382319C185592680 @default.
• W1567382319 hasConceptScore W1567382319C2107291 @default.
• W1567382319 hasConceptScore W1567382319C2781322055 @default.
• W1567382319 hasConceptScore W1567382319C62478195 @default.
• W1567382319 hasConceptScore W1567382319C75217442 @default.
• W1567382319 hasConceptScore W1567382319C86803240 @default.
• W1567382319 hasConceptScore W1567382319C90934575 @default.
• W1567382319 hasConceptScore W1567382319C95444343 @default.
• W1567382319 hasConceptScore W1567382319C97029542 @default.
• W1567382319 hasIssue "5" @default.
• W1567382319 hasLocation W15673823191 @default.
• W1567382319 hasOpenAccess W1567382319 @default.
• W1567382319 hasPrimaryLocation W15673823191 @default.
• W1567382319 hasRelatedWork W1567382319 @default.
• W1567382319 hasRelatedWork W2025452552 @default.
• W1567382319 hasRelatedWork W2026337844 @default.
• W1567382319 hasRelatedWork W2105863578 @default.
• W1567382319 hasRelatedWork W2123013129 @default.
• W1567382319 hasRelatedWork W2140851951 @default.
• W1567382319 hasRelatedWork W2156730370 @default.
• W1567382319 hasRelatedWork W2462011189 @default.
• W1567382319 hasRelatedWork W2766294138 @default.
• W1567382319 hasRelatedWork W4313642509 @default.
• W1567382319 hasVolume "273" @default.
• W1567382319 isParatext "false" @default.
• W1567382319 isRetracted "false" @default.
• W1567382319 magId "1567382319" @default.
• W1567382319 workType "article" @default.