Sodium orthovanadate induced tyrosine phosphorylation of platelet nitric oxide synthase negatively regulates enzyme activity

Milward, Andrew; Riba, Rocio; Patel, B.; Oberprieler, Nikolaus G.; Naseem, Khalid M.

doi:10.1016/j.bbagen.2006.06.004

Cited by 8 publications

(11 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous data suggest that these mechanisms might be different and dependent on the NO concentration within the extracellular versus intracellular compartments (Jenei et al, 2006). The extent to which NO plays a role in biological functions varies across cell types and their organ of origin (Milward et al, 2006); therefore, the role of integrin-α9β1-and NO-mediated cell migration might vary considerably for any given organ system. Our findings suggest that integrin-α9β1-dependent NO might be important in the case of neutrophils, in which integrin α9β1 is highly expressed and plays an important functional role during granulopoiesis and neutrophil migration (Shang et al, 1999;Ross et al, 2006;Chen et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The enzyme iNOS is known to interact with Rho GTPases, including Rac-1 (Kuncewicz et al, 2001), and NO itself can act as a heme cofactor for guanylyl cyclase (GC) generating cGMP, a second messenger acting coordinately to facilitate cell migration. The biological effects of NO are contextand cell-type-specific, resulting from either increased or decreased NOS activity (Pan et al, 1996;Fulton et al, 2005;Hausel et al, 2006;Milward et al, 2006). The enzymatic activity of NOS is often modulated by phosphorylation and/or its direct interactions with other intracellular proteins such as Src tyrosine kinases and Erk mitogen-activated protein (MAP) kinase (Kone et al, 2003;Korhonen et al, 2005;Zhang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Integrin α9β1 mediates enhanced cell migration through nitric oxide synthase activity regulated by Src tyrosine kinase

Gupta

Vlahakis

2009

Journal of Cell Science

View full text Add to dashboard Cite

Integrins are important mediators of cell adhesion and migration, which in turn are essential for diverse biological functions, including wound healing and cancer metastasis. The integrin α9β1 is expressed on numerous mammalian tissues and can mediate accelerated cell migration. As the molecular signaling mechanisms that transduce this effect are poorly defined, we investigated the pathways by which activated integrin α9β1 signals migration. We found for the first time that specific ligation of integrin α9β1 rapidly activates Src tyrosine kinase, with concomitant tyrosine phosphorylation of p130Cas and activation of Rac-1. Furthermore, activation of integrin α9β1 also enhanced NO production through activation of inducible nitric oxide synthase (iNOS). Inhibition of Src tyrosine kinase or NOS decreased integrin-α9β1-dependent cell migration. Src appeared to function most proximal in the signaling cascade, in a FAK-independent manner to facilitate iNOS activation and NO-dependent cell migration. The cytoplasmic domain of integrin α9 was crucial for integrin-α9β1-induced Src activation, subsequent signaling events and cell migration. When taken together, our results describe a novel and unique mechanism of coordinated interactions of the integrin α9 cytoplasmic domain, Src tyrosine kinase and iNOS to transduce integrin-α9β1-mediated cell migration.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrin α9β1 mediates enhanced cell migration through nitric oxide synthase activity regulated by Src tyrosine kinase

Gupta

Vlahakis

2009

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Figure 8C shows that total PTP activity increased during the refilling cycle, being the highest at 30 days, the time for maximal loading with NO (as demonstrated in Figure 1 for NOS). Salivary gland PTP activity is highly inhibited by sodium orthovanadate (SO), which is a classical inhibitor of PTPs [29], [30], [31], [32], [33]. Furthermore, injection of the insects with Tc GIPL decreased PTP activity in glands (Figure 8D).…”

Section: Resultsmentioning

confidence: 99%

“…Studies in the literature have pointed out the role of protein tyrosine phosphatases (PTPs) in the regulation of NO synthesis [29], [30], [32]. The PTPs are key mediators of phosphotyrosine levels inside cells and are commonly manipulated by invading pathogens [49].…”

Section: Discussionmentioning

confidence: 99%

Glycoinositolphospholipids from Trypanosomatids Subvert Nitric Oxide Production in Rhodnius prolixus Salivary Glands

et al. 2012

View full text Add to dashboard Cite

Background Rhodnius prolixus is a blood-sucking bug vector of Trypanosoma cruzi and T. rangeli. T. cruzi is transmitted by vector feces deposited close to the wound produced by insect mouthparts, whereas T. rangeli invades salivary glands and is inoculated into the host skin. Bug saliva contains a set of nitric oxide-binding proteins, called nitrophorins, which deliver NO to host vessels and ensure vasodilation and blood feeding. NO is generated by nitric oxide synthases (NOS) present in the epithelium of bug salivary glands. Thus, T. rangeli is in close contact with NO while in the salivary glands.Methodology/Principal FindingsHere we show by immunohistochemical, biochemical and molecular techniques that inositolphosphate-containing glycolipids from trypanosomatids downregulate NO synthesis in the salivary glands of R. prolixus. Injecting insects with T. rangeli-derived glycoinositolphospholipids (Tr GIPL) or T. cruzi-derived glycoinositolphospholipids (Tc GIPL) specifically decreased NO production. Salivary gland treatment with Tc GIPL blocks NO production without greatly affecting NOS mRNA levels. NOS protein is virtually absent from either Tr GIPL- or Tc GIPL-treated salivary glands. Evaluation of NO synthesis by using a fluorescent NO probe showed that T. rangeli-infected or Tc GIPL-treated glands do not show extensive labeling. The same effect is readily obtained by treatment of salivary glands with the classical protein tyrosine phosphatase (PTP) inhibitor, sodium orthovanadate (SO). This suggests that parasite GIPLs induce the inhibition of a salivary gland PTP. GIPLs specifically suppressed NO production and did not affect other anti-hemostatic properties of saliva, such as the anti-clotting and anti-platelet activities.Conclusions/SignificanceTaken together, these data suggest that trypanosomatids have overcome NO generation using their surface GIPLs. Therefore, these molecules ensure parasite survival and may ultimately enhance parasite transmission.

show abstract

“…Association of SHP-1 with eNOS was confirmed in both resting and thrombin-activated platelets, but it was not 2204 HENEBERG detected in the endothelial cells (68). Platelet treatment with 0.1-1.0 mM sodium orthovanadate was shown to increase tyrosine phosphorylation of eNOS, leading to the decrease of basal eNOS activity and the blunting of thrombin-induced guanosine 3¢,5¢-monophosphate (cGMP) formation; the vanadate-induced changes were abolished when the platelets were preincubated with the Src kinase inhibitor PP2, but not by the PKC inhibitor Ro-31-8220 or PI3K inhibitor wortmannin (61). In central nervous system glia, SHP-1 was shown to inversely regulate iNOS and arginase I and to control virus infection.…”

Section: Multiple Roles Of Shp-1 In No Productionmentioning

confidence: 99%

Reactive Nitrogen Species and Hydrogen Sulfide as Regulators of Protein Tyrosine Phosphatase Activity

Heneberg

2014

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Significance: Redox modifications of thiols serve as a molecular code enabling precise and complex regulation of protein tyrosine phosphatases (PTPs) and other proteins. Particular gasotransmitters and even the redox modifications themselves affect each other, of which a typical example is S-nitrosylation-mediated protection against the further oxidation of protein thiols. Recent Advances: For a long time, PTPs were considered constitutively active housekeeping enzymes. This view has changed substantially over the last two decades, and the PTP family is now recognized as a group of tightly and flexibly regulated fundamental enzymes. In addition to the conventional ways in which they are regulated, including noncovalent interactions, phosphorylation, and oxidation, the evidence that has accumulated during the past two decades suggests that many of these enzymes are also modulated by gasotransmitters, namely by nitric oxide (NO) and hydrogen sulfide (H 2 S). Critical Issues: The specificity and selectivity of the methods used to detect nitrosylation and sulfhydration remains to be corroborated, because several researchers raised the issue of false-positive results, particularly when using the most widespread biotin switch method. Further development of robust and straightforward proteomic methods is needed to further improve our knowledge of the full extent of the gasotransmitters-mediated changes in PTP activity, selectivity, and specificity. Further Directions: Results of the hitherto performed studies on gasotransmitter-mediated PTP signaling await translation into clinical medicine and pharmacotherapeutics. In addition to directly affecting the activity of particular PTPs, the use of reversible S-nitrosylation as a protective mechanism against oxidative stress should be of high interest. Antioxid. Redox Signal. 20, 2191-2209.

show abstract

Sodium orthovanadate induced tyrosine phosphorylation of platelet nitric oxide synthase negatively regulates enzyme activity

Cited by 8 publications

References 26 publications

Integrin α9β1 mediates enhanced cell migration through nitric oxide synthase activity regulated by Src tyrosine kinase

Integrin α9β1 mediates enhanced cell migration through nitric oxide synthase activity regulated by Src tyrosine kinase

Glycoinositolphospholipids from Trypanosomatids Subvert Nitric Oxide Production in Rhodnius prolixus Salivary Glands

Reactive Nitrogen Species and Hydrogen Sulfide as Regulators of Protein Tyrosine Phosphatase Activity

Contact Info

Product

Resources

About