Platelet‐derived growth factor activates production of reactive oxygen species by NAD(P)H‐oxidase in smooth muscle cells through Gi1,2

Kreuzer, Jörg; Viedt, Christiane; Brandes, Ralf P.; Seeger, Fabian; Rosenkranz, Anna; Sauer, Heinrich; Бабич, А. А.; Nürnberg, Bernd; Kather, H; Krieger-Brauer, Heidemarie I.

doi:10.1096/fj.01-1036fje

Cited by 77 publications

(45 citation statements)

References 56 publications

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“…14 Pretreatment of quiescent SMCs with PTX (100 ng/mL, 16 hours) did not show any significant effects on PDGF-BBinduced Egr-1 binding activity. This observation is in line with our previous observation and underscores the differences in PDGF-AA and PDGF-BB signaling.…”

Section: Pdgf-bb-induced Egr-1 Activation Is Tyrosine Kinase and Src-mentioning

confidence: 85%

Platelet-Derived Growth Factor Induces Tissue Factor Expression in Vascular Smooth Muscle Cells via Activation of Egr-1

et al. 2004

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Abstract-Activation of vascular smooth muscle cells (SMCs) by platelet-derived growth factor (PDGF) is a seminal event in the initiation and progression of the atherosclerotic lesion and may contribute to atherosclerotic plaque instability with plaque rupture and thrombus formation. Tissue factor (TF), a prothrombotic molecule expressed by various cell types within atherosclerotic plaques, is thought to play a major role in thrombus formation after plaque rupture. This study examined intracellular signaling pathways leading to TF expression and Egr-1 activation, a key element in tissue factor transcription, by PDGF-BB in rat SMCs. PDGF-BB induced TF mRNA and protein expression in a time-dependent manner. Early growth response factor-1 (Egr-1) binding activity was also induced by PDGF-BB, as well as phosphorylation of extracellular signal-regulated kinase. PDGF-BB-induced Egr-1 activation was suppressed by inhibitors of 2 upstream activators of Egr-1, extracellular signal-regulated kinase (ERK) and Src family kinases, whereas antioxidants, phosphatidylinositol 3-phosphate kinase, and p38 MAPK inhibitors had no effect. PDGF-BB-stimulated expression of the transcriptional co-repressor NAB2 was time-dependent. Furthermore, transient transfections of SMCs with wild-type and mutated TF promoter constructs showed that the Egr-1 binding region is an important transcriptional regulator of PDGF-BB-induced TF expression. Taken together, the results suggest that PDGF-BB induces TF expression and activity in SMC by a Src family kinases/ERK/Egr-1 signaling pathway and may therefore contribute to thrombus formation in advanced atherosclerosis and restenosis.

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Section: Pdgf-bb-induced Egr-1 Activation Is Tyrosine Kinase and Src-mentioning

confidence: 85%

Platelet-Derived Growth Factor Induces Tissue Factor Expression in Vascular Smooth Muscle Cells via Activation of Egr-1

et al. 2004

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“…Therefore, we conclude that Nox4 recruitment to SHPS-1 is an important step leading to IGF-Istimulated VSMC proliferation. Although ROS has been proposed to mediate growth factor-stimulated signaling (26) and NADPH oxidases were involved in PDGF-induced ROS generation (27), this is the first study to demonstrate, in vitro and in vivo, how a growth factor, IGF-I, modulates ROS generation on a specific molecular scaffold to mediate increased downstream signaling and biological actions.…”

Section: Function Of Shps-1-localized Nox4mentioning

confidence: 87%

Recruitment of Nox4 to a Plasma Membrane Scaffold Is Required for Localized Reactive Oxygen Species Generation and Sustained Src Activation in Response to Insulin-like Growth Factor-I

Shen

Wai

et al. 2013

Journal of Biological Chemistry

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Background: Nox4-derived ROS is required for Src oxidation and activation. Results: Grb2 recruits Nox4 to the scaffold protein SHPS-1, and Nox4 colocalization with Src on SHPS-1 allows Nox4 to activate Src. Conclusion: Nox4 recruitment to SHPS-1 is essential for sustained Src activation and cell proliferation. Significance: This is the first report that localized ROS generation mediates growth factor signaling in vitro and in vivo.

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“…As described above, PDGF is involved in signaling from myotome to sclerotome during rib development, and activation of PDGFRα, a receptor tyrosine kinase, on sclerotome cells leads to altered cell migration via a PI3 kinase-Akt pathway (40). Gα i3 is known to regulate migration of HeLa cells by an Aktdependent pathway (41), and a growing body of data indicates that heterotrimeric G proteins can function within receptor tyrosine kinase signaling pathways (42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

Development of the mammalian axial skeleton requires signaling through the Gα _i subfamily of heterotrimeric G proteins

Plummer

Spicher

Malphurs

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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129/SvEv mice with a loss-of-function mutation in the heterotrimeric G protein α-subunit gene Gnai3 have fusions of ribs and lumbar vertebrae, indicating a requirement for Gα i (the "inhibitory" class of α-subunits) in somite derivatives. Mice with mutations of Gnai1 or Gnai2 have neither defect, but loss of both Gnai3 and one of the other two genes increases the number and severity of rib fusions without affecting the lumbar fusions. No myotome defects are observed in Gnai3/Gnai1 double-mutant embryos, and crosses with a conditional allele of Gnai2 indicate that Gα i is specifically required in cartilage precursors. Penetrance and expressivity of the rib fusion phenotype is altered in mice with a mixed C57BL/6 × 129/SvEv genetic background. These phenotypes reveal a previously unknown role for G protein-coupled signaling pathways in development of the axial skeleton.mouse | thoracic | sternum | lateral plate mesoderm T he heterotrimeric G protein α-subunits, encoded by 16 paralogous genes in humans and mice, are cytoplasmic proteins that couple a wide variety of cell-surface receptors to intracellular effectors, such as ion channels and enzymes (1-3). The complex signal-transduction activity of these widely expressed proteins has long been studied at the biochemical and cellular level, but their role in development of whole organisms is less well understood. The "inhibitory" class of α subunits (Gα i ), originally named for its ability to inhibit adenylyl cyclase activity, is encoded by the Gnai1, Gnai2, and Gnai3 genes. The three Gα i subunits share 85-95% amino acid sequence identity, and they form a subfamily with the neuronal α-subunit (Gα o /Gnao), the transducin α-subunits expressed in rod (Gα t-r /Gnat1) and cone cells (Gα t-c /Gnat2), and gustducin (Gα gust /Gnat3) expressed in taste buds. The Gα i genes are linked in pairs with the transducin and gustducin genes on mouse chromosomes 3, 5, and 9. This linkage, together with their sequence homology, suggests that these subunits evolved from an ancestral G protein gene by a tandem duplication followed by two block duplications (3). A G αi ortholog is present in Drosophila, and identification of transducin genes in the lamprey genome indicates that the initial duplication to form an ancestral G αi and G αt gene predates the evolution of gnathostomes (4).Targeted loss-of-function mutations of all three Gα i genes have been generated in mice, and the resulting phenotypes indicate that Gnai1 and Gnai2 have gene-specific functions in a wide variety of tissues: loss of Gnai1 affects long-term memory (5), and Gnai2 knockout mice spontaneously develop an inflammatory bowel disease resembling ulcerative colitis (6) and have altered heart rate dynamics (7). Initial analyses of Gnai3 knockout mice did not reveal an associated phenotype (8, 9), but more recently Gnai3 has been shown to be required for insulinmediated regulation of autophagy in hepatocytes (10). Comparison of Gnai2 knockouts and Gnai3/Gnai1 double-knockouts suggests that the three Gα i proteins may al...

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Platelet‐derived growth factor activates production of reactive oxygen species by NAD(P)H‐oxidase in smooth muscle cells through Gi1,2

Cited by 77 publications

References 56 publications

Platelet-Derived Growth Factor Induces Tissue Factor Expression in Vascular Smooth Muscle Cells via Activation of Egr-1

Platelet-Derived Growth Factor Induces Tissue Factor Expression in Vascular Smooth Muscle Cells via Activation of Egr-1

Recruitment of Nox4 to a Plasma Membrane Scaffold Is Required for Localized Reactive Oxygen Species Generation and Sustained Src Activation in Response to Insulin-like Growth Factor-I

Development of the mammalian axial skeleton requires signaling through the Gα _i subfamily of heterotrimeric G proteins

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Platelet‐derived growth factor activates production of reactive oxygen species by NAD(P)H‐oxidase in smooth muscle cells through Gi1,2

Cited by 77 publications

References 56 publications

Platelet-Derived Growth Factor Induces Tissue Factor Expression in Vascular Smooth Muscle Cells via Activation of Egr-1

Platelet-Derived Growth Factor Induces Tissue Factor Expression in Vascular Smooth Muscle Cells via Activation of Egr-1

Recruitment of Nox4 to a Plasma Membrane Scaffold Is Required for Localized Reactive Oxygen Species Generation and Sustained Src Activation in Response to Insulin-like Growth Factor-I

Development of the mammalian axial skeleton requires signaling through the Gα i subfamily of heterotrimeric G proteins

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Development of the mammalian axial skeleton requires signaling through the Gα _i subfamily of heterotrimeric G proteins