Nitration of PECAM-1 ITIM tyrosines abrogates phosphorylation and SHP-2 binding

Newman, Debra K.; Hoffman, Sara M.; Kotamraju, Srigiridhar; Zhao, Tieming; Wakim, Bassam T.; Kalyanaraman, Balaraman; Newman, Peter J.

doi:10.1016/s0006-291x(02)02060-0

Cited by 35 publications

(24 citation statements)

References 30 publications

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“…Several reports suggest that nitration prevents phosphorylation of specific tyrosine residues (35,(39)(40)(41)(42)(43). ␣-Actinin is closely associated with both transmembrane adhesion receptors and cytoskeletal proteins and, thus, may be an attractive regulatory target.…”

Section: Discussionmentioning

confidence: 99%

Cyclic GMP-independent mechanisms contribute to the inhibition of platelet adhesion by nitric oxide donor: A role for α-actinin nitration

Marcondes

Cardoso

Morganti

et al. 2006

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

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The nitric oxide-mediated actions are mostly due to cyclic GMP (cGMP) formation, but cGMP-independent mechanisms, such as tyrosine nitration, have been suggested as potential signaling pathways modulating the NO-induced responses. However, the mechanisms that lead to tyrosine nitration in platelets are poorly studied, and the protein targets of nitration have not been identified in these cells. Therefore, we have used the model of platelet adhesion to fibrinogen-coated plates to investigate the cGMPindependent mechanisms of the NO-donor sodium nitroprusside (SNP) that leads to inhibition of platelet adhesion. SNP concentration-dependently inhibited platelet adhesion, as observed at 15-min and 60-min adhesion. Additionally, SNP markedly increased the cGMP levels, and the soluble guanylate inhibitor ODQ nearly abolished the SNP-mediated cGMP elevations in all experimental conditions used. Nevertheless, ODQ failed to affect the adhesion inhibition obtained with 1.0 mM SNP at 15 min. On the other hand, superoxide dismutase or peroxynitrite (ONOO ؊ ) scavenger epigallocatechin gallate significantly reversed the inhibition of platelet adhesion by SNP (1 mM, 15 min). Western blot analysis in SNP (1 mM, 15 min)-treated platelets showed a single tyrosine-nitrated protein with an apparent mass of Ϸ105 kDa. Nanospray LC-MS͞MS identified the human ␣-actinin 1 cytoskeletal isoform (P12814) as the protein contained in the nitrated SDS gel band. Thus, tyrosine nitration of ␣-actinin, through ONOO ؊ formation, may be a key modulatory mechanism to control platelet adhesion.protein nitration ͉ sodium nitroprusside ͉ peroxynitrite ͉ human platelet ͉ soluble guanylate cyclase B lood platelets play a key role in maintaining the integrity of the vascular system through their ability to arrest bleeding and to promote repair of injured blood vessels (1). Platelet adhesion is the first step to begin the haemostatic process, and fibrinogen is responsible to mediate both platelet adhesion and aggregation through binding to the platelet membrane glycoprotein IIb-IIIa (integrin ␣ IIb ␤ 3 ) (2). In nonactivated platelets, the majority of GPIIb͞IIIa is in a low-affinity state. However, they are capable of binding directly to immobilized fibrinogen and von Willebrand factor, because in this nonactivated state, the platelets attach to domains of fibrinogen distinct of those seen after platelet activation (3).The nitric oxide (NO)-dependent inhibition of platelet adhesion to the subendothelium is essential in preventing excessive aggregation and thrombus formation. It is well accepted that NO-mediated actions are due to activation of the soluble guanylate cyclase leading to an increase of cyclic GMP (cGMP; ref. 4). The NO donor sodium nitroprusside (SNP) has been shown to spontaneously release NO for prolonged time periods (5, 6), leading to inhibition of platelet adhesion in vivo (7) and in vitro (8,9). Although the reduction of platelet adhesion by SNP is accompanied by increased cGMP levels, cGMP-independent mechanisms have also been proposed...

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Section: Discussionmentioning

confidence: 99%

Cyclic GMP-independent mechanisms contribute to the inhibition of platelet adhesion by nitric oxide donor: A role for α-actinin nitration

Marcondes

Cardoso

Morganti

et al. 2006

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

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“…Antibodies-Domain-specific mouse anti-human PECAM-1 monoclonal antibodies (mAbs) used in this study include: 235.1 (specific for the PECAM-1 C-terminal 15 amino acids), PECAM-1.2 (specific for PECAM-1 Ig Domain 6), PECAM-1.3 (specific for PECAM-1 Ig Domain 1), and have been previously described (23,35,36). Normal mouse IgG and secondary antibodies were purchased from Invitrogen (Grand Island, NY).…”

Section: Methodsmentioning

confidence: 99%

Regulation of Endothelial Cell Barrier Function by Antibody-driven Affinity Modulation of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1)

Mei

Campbell

Paddock

et al. 2014

Journal of Biological Chemistry

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Background: PECAM-1 participates in adhesion and signaling in blood and vascular cells. Results:The adhesive properties of PECAM-1 in both cellular and artificial membranes can be regulated. Conclusion:The binding affinity of PECAM-1 can be regulated by engagement of membrane-proximal Ig domain 6. Significance: Modulating the adhesive properties of PECAM-1 offers possibility to control endothelial cell migration and barrier function in vascular permeability disorders.

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“…Proteins reported to be able to associate with the PECAM-1 cytoplasmic domain are summarized in Table 2; however, it is important to recognize that the extent to which these potential binding partners interact with PECAM-1 is likely to be influenced by their relative local concentrations, their relative binding affinities, and the effect of additional posttranslational modifications of the PECAM-1 cytoplasmic domain. 56 The protein most commonly reported to interact with the PECAM-1 cytoplasmic domain is the SH2 domain-containing protein-tyrosine phosphatase, SHP-2. It is widely accepted that phosphorylation of the PECAM-1 ITIM tyrosine residues results in both recruitment and activation of SHP-2.…”

Section: Cytoplasmic Proteins That Bind Tyrosine Phosphorylated Pecam-1mentioning

confidence: 99%

Signal Transduction Pathways Mediated by PECAM-1

Newman

2003

ATVB

342

195

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Abstract-Recent studies of platelet endothelial cell adhesion molecule-1 (PECAM-1 [CD31])-deficient mice have revealed that this molecule plays an important role in controlling the activation and survival of cells on which it is expressed. In this review, we focus on the complex cytoplasmic domain of PECAM-1 and describe what is presently known about its structure, posttranslational modifications, and binding partners. In addition, we summarize findings that implicate PECAM-1 as an inhibitor of cellular activation via protein tyrosine kinase-dependent signaling pathways, an activator of integrins, and a suppressor of cell death via pathways that depend on damage to the mitochondria. The challenge of future research will be to bridge our understanding of the functional and biochemical properties

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Nitration of PECAM-1 ITIM tyrosines abrogates phosphorylation and SHP-2 binding

Cited by 35 publications

References 30 publications

Cyclic GMP-independent mechanisms contribute to the inhibition of platelet adhesion by nitric oxide donor: A role for α-actinin nitration

Cyclic GMP-independent mechanisms contribute to the inhibition of platelet adhesion by nitric oxide donor: A role for α-actinin nitration

Regulation of Endothelial Cell Barrier Function by Antibody-driven Affinity Modulation of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1)

Signal Transduction Pathways Mediated by PECAM-1

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