Lysyl Oxidase Oxidizes Cell Membrane Proteins and Enhances the Chemotactic Response of Vascular Smooth Muscle Cells

Lucero, Héctor A.; Ravid, Katya; Grimsby, Jessica L.; Rich, Celeste B.; DiCamillo, Sandra J.; Mäki, Joni M.; Myllyharju, Johanna; Kagan, Herbert M.

doi:10.1074/jbc.m709897200

Cited by 78 publications

(97 citation statements)

References 53 publications

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“…Supporting a positive role for ROS on SHP2 activation, evidence shows that oxidative stress induces tyrosine phosphorylation of SHP2 at the C terminus through a mechanism involving the formation of lipid rafts and caveolin1 expression (39,40). Similar results have been demonstrated in response to exogenous hydrogen peroxide treatment (55) and the inhibition of lysyl oxidase (56).…”

Section: Discussionsupporting

confidence: 71%

Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Wang

Chen

Sheu

et al. 2014

The Journal of Immunology

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Helicobacter pylori infection not only induces gastric inflammation but also increases the risk of gastric tumorigenesis. IFN-γ has antimicrobial effects; however, H. pylori infection elevates IFN-γ–mediated gastric inflammation and may suppress IFN-γ signaling as a strategy to avoid immune destruction through an as-yet-unknown mechanism. This study was aimed at investigating the mechanism of H. pylori–induced IFN-γ resistance. Postinfection of viable H. pylori decreased IFN-γ–activated signal transducers and activators of transcription 1 and IFN regulatory factor 1 not only in human gastric epithelial MKN45 and AZ-521 but also in human monocytic U937 cells. H. pylori caused an increase in the C-terminal tyrosine phosphorylation of Src homology-2 domain–containing phosphatase (SHP) 2. Pharmacologically and genetically inhibiting SHP2 reversed H. pylori–induced IFN-γ resistance. In contrast to a clinically isolated H. pylori strain HP238, the cytotoxin-associated gene A (CagA) isogenic mutant strain HP238CagAm failed to induce IFN-γ resistance, indicating that CagA regulates this effect. Notably, HP238 and HP238CagAm differently caused SHP2 phosphorylation; however, imaging and biochemical analyses demonstrated CagA-mediated membrane-associated binding with phosphorylated SHP2. CagA-independent generation of reactive oxygen species (ROS) contributed to H. pylori–induced SHP2 phosphorylation; however, ROS/SHP2 mediated IFN-γ resistance in a CagA-regulated manner. This finding not only provides an alternative mechanism for how CagA and ROS coregulate SHP2 activation but may also explain their roles in H. pylori–induced IFN-γ resistance.

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Section: Discussionsupporting

confidence: 71%

Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Wang

Chen

Sheu

et al. 2014

The Journal of Immunology

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“…LOXmediated migration is correlated with Src and FAK phosphorylation because of hydrogen peroxyde generation 38 or of oxidation of cell surface receptors. 40 Multiple levels of cell-ECM interactions are potentially involved in capillary formation. Here, we demonstrate that col4a1 …”

Section: Discussionmentioning

confidence: 99%

Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane

Bignon

Pichol-Thievend

Hardouin

et al. 2011

Blood

171

173

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Sprouting angiogenesis is associated with extensive extracellular matrix (ECM) remodeling. The molecular mechanisms involved in building the vascular microenvironment and its impact on capillary formation remain elusive. We therefore performed a proteomic analysis of ECM from endothelial cells maintained in hypoxia, a major stimulator of angiogenesis. Here, we report the characterization of lysyl oxidase-like protein-2 (LOXL2) as a hypoxia-target expressed in neovessels and accumulated in the endothelial ECM. IntroductionAngiogenesis occurs during development and tissue remodeling, and in the pathologic context of cardiovascular ischemic diseases or tumor growth. Sprouting of new vessels is initiated by stimulation of endothelial cells (ECs) by a combination of signals from the microenvironment that includes oxygen tension and growth factors. Cells from not yet vascularized tissue and ECs that invade this microenvironment are both hypoxia targets through the Hypoxia Inducible Factor (HIF) pathway. HIF activates transcription of genes coding for autocrine/paracrine factors like vascular endothelial growth factor (VEGF) and extracellular matrix (ECM) components. 1 Synergy between these responses is assumed through local concentration of growth factors in the ECM where they function as attractant for ECs. Specialized ECs, called tip cells, lead vascular growth by sending out filopodia to explore the hypoxic microenvironment. 2 Tip cells are thus continuously exposed to low oxygen concentration. 3 Stalk cells, located behind the tip cells, serve to vessel growth by proliferation, lumen formation and junction establishment. 4 Vascular ECM undergoes major remodeling during angiogenesis, consisting in ECM/basement membrane degradation, provisional ECM generation and assembly of a new basement membrane. ECM-mediated mechanotransductive signaling regulates 3D multicellular organization, including lumen formation and tubulogenesis. Thus, in addition to storing angiogenic factors and providing structural features, ECM is a dynamic promoter of angiogenesis. 5 Subendothelial basement membrane is composed of nonfibrillar collagen IV, laminin, perlecan and nidogens. Other collagens (VIII, XV, and XVIII), fibronectin and matricellular proteins (thrombospondin-1, Cyr61) are associated with the basement membrane. There is only little data concerning the assembly of the vascular microenvironment and its impact on angiogenesis. Genes encoding ECM components and enzymes involved in their assembly and stabilization are targets of hypoxia in ECs. 1 To identify key regulators of the angiogenesis-associated ECM remodeling, we performed a proteomic analysis of endothelial ECM generated in vitro under hypoxic conditions. We found that the ECM cross-linking enzyme, lysyl oxidase-like protein-2 (LOXL2) is a major target of hypoxia. Lysyl oxidases, consisting in lysyl oxidase (LOX) and 4 lysyl oxidase-like proteins (LOXL 1 to 4), catalyze the deamination of lysines and hydroxylysines, generating aldehydes that spontaneously react to form co...

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“…In parallel studies, highly purified human sVAP-1 induced dose-dependent migration of peripheral blood lymphocytes in Boyden chamber assays with a maximal response between 10 and 100 ng/ml ( Figure 3G) that was comparable to that seen with 10 ng/ml CXCL12, a potent lymphocyte chemotactic factor. The related amine oxidase LOX has been shown to promote the migration of smooth muscle cells and monocytes through the action of H 2 O 2 (33,34), and a recent study in zebrafish reported that H 2 O 2 produced by an unspecified amine oxidase promotes leukocyte recruitment during wound healing (35). This led us to investigate whether the promigratory effects VAP-1 deficiency attenuates leukocyte infiltration into the liver during fibrogenesis.…”

Section: Circulating Serum [Svap-1] Is Significantly Elevated In Humamentioning

confidence: 99%

Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis

Weston¹,

Shepherd²,

Claridge³

et al. 2014

J. Clin. Invest.

188

205

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Lysyl Oxidase Oxidizes Cell Membrane Proteins and Enhances the Chemotactic Response of Vascular Smooth Muscle Cells

Cited by 78 publications

References 53 publications

Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane

Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis

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