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Vanadium Compounds as Pro-Inflammatory Agents: Effects on Cyclooxygenases.

Korbecki J, Baranowska-Bosiacka I, Gutowska I, Chlubek D - Int J Mol Sci (2015)

Bottom Line: We refer mainly to the effects of vanadate (orthovanadate), vanadyl and pervanadate ions; the main focus is placed on their impact on intracellular signaling.We describe the exact mechanism of the effect of vanadium compounds on protein tyrosine phosphatases (PTP), epidermal growth factor receptor (EGFR), PLCγ, Src, mitogen-activated protein kinase (MAPK) cascades, transcription factor NF-κB, the effect on the proteolysis of COX-2 and the activity of cPLA2.For a better understanding of these processes, a lot of space is devoted to the transformation of vanadium compounds within the cell and the molecular influence on the direct targets of the discussed vanadium compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111 Szczecin, Poland. jan.korbecki@onet.eu.

ABSTRACT
This paper discusses how the activity and expression of cyclooxygenases are influenced by vanadium compounds at anticancer concentrations and recorded in inorganic vanadium poisonings. We refer mainly to the effects of vanadate (orthovanadate), vanadyl and pervanadate ions; the main focus is placed on their impact on intracellular signaling. We describe the exact mechanism of the effect of vanadium compounds on protein tyrosine phosphatases (PTP), epidermal growth factor receptor (EGFR), PLCγ, Src, mitogen-activated protein kinase (MAPK) cascades, transcription factor NF-κB, the effect on the proteolysis of COX-2 and the activity of cPLA2. For a better understanding of these processes, a lot of space is devoted to the transformation of vanadium compounds within the cell and the molecular influence on the direct targets of the discussed vanadium compounds.

No MeSH data available.


Related in: MedlinePlus

The proposed mechanism of c-Src activation of vanadium compounds. (a) c-Src is activated by the dephosphorylation of Tyr527 by PTPs. This stage is followed by the cross-autophosphorylation of c-Src at Tyr416 which results in the activation of these kinases; (b) Part of the c-Src pool in the inactive form is cross-autophosphorylated and occurs in the double phosphorylated form, at Tyr527 and Tyr416. Phosphorylation at Tyr416 is abolished by PTPs. Vanadium compounds as inhibitors of PTP cause the accumulation of the double-phosphorylated form. This form may be oxidized by pervanadate. In this process, a disulfide bond is created between Cys487 and Cys245, which destabilizes the inactive structure of c-Src by abolishing the binding of SH2 with phosphorylated Tyr527.
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ijms-16-12648-f004: The proposed mechanism of c-Src activation of vanadium compounds. (a) c-Src is activated by the dephosphorylation of Tyr527 by PTPs. This stage is followed by the cross-autophosphorylation of c-Src at Tyr416 which results in the activation of these kinases; (b) Part of the c-Src pool in the inactive form is cross-autophosphorylated and occurs in the double phosphorylated form, at Tyr527 and Tyr416. Phosphorylation at Tyr416 is abolished by PTPs. Vanadium compounds as inhibitors of PTP cause the accumulation of the double-phosphorylated form. This form may be oxidized by pervanadate. In this process, a disulfide bond is created between Cys487 and Cys245, which destabilizes the inactive structure of c-Src by abolishing the binding of SH2 with phosphorylated Tyr527.

Mentions: The activation and inhibition of Src involve PTPs which dephosphorylate tyrosine residues, significant for the regulation of these kinases. In addition, important in the regulation of Src activity are SH2 domains, which recognize phosphotyrosine residues and thus stabilize the inactive conformation of Src. The structure of Src contains two tyrosine residues that are key for the regulation of this family of kinases (Figure 4) [73,74]. In c-Src these are Tyr527 and Tyr416. After the phosphorylation of c-Src Tyr527, the SH2 domain of this protein binds to c-Src P-Tyr527, stabilizing the inactive conformation of c-Src. The activation of this kinase family consists in the dephosphorylation of P-Tyr527 by various PTPs [73]. After the dephosphorylation of c-Src Tyr527, this kinase is in the intermediate conformation, between the active and inactive conformation. Then cross-autophosphorylation occurs by another c-Src, at Tyr416, which induces a conformational change and the full activation of the enzyme [74,75]. c-Src inactivation involves PTP-induced dephosphorylation of residues of c-Src P-Tyr416 and phosphorylation of c-Src Tyr527 by different kinases [74]. After this modification the SH2 domain stabilizes the inactive conformation of c-Src.


Vanadium Compounds as Pro-Inflammatory Agents: Effects on Cyclooxygenases.

Korbecki J, Baranowska-Bosiacka I, Gutowska I, Chlubek D - Int J Mol Sci (2015)

The proposed mechanism of c-Src activation of vanadium compounds. (a) c-Src is activated by the dephosphorylation of Tyr527 by PTPs. This stage is followed by the cross-autophosphorylation of c-Src at Tyr416 which results in the activation of these kinases; (b) Part of the c-Src pool in the inactive form is cross-autophosphorylated and occurs in the double phosphorylated form, at Tyr527 and Tyr416. Phosphorylation at Tyr416 is abolished by PTPs. Vanadium compounds as inhibitors of PTP cause the accumulation of the double-phosphorylated form. This form may be oxidized by pervanadate. In this process, a disulfide bond is created between Cys487 and Cys245, which destabilizes the inactive structure of c-Src by abolishing the binding of SH2 with phosphorylated Tyr527.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490466&req=5

ijms-16-12648-f004: The proposed mechanism of c-Src activation of vanadium compounds. (a) c-Src is activated by the dephosphorylation of Tyr527 by PTPs. This stage is followed by the cross-autophosphorylation of c-Src at Tyr416 which results in the activation of these kinases; (b) Part of the c-Src pool in the inactive form is cross-autophosphorylated and occurs in the double phosphorylated form, at Tyr527 and Tyr416. Phosphorylation at Tyr416 is abolished by PTPs. Vanadium compounds as inhibitors of PTP cause the accumulation of the double-phosphorylated form. This form may be oxidized by pervanadate. In this process, a disulfide bond is created between Cys487 and Cys245, which destabilizes the inactive structure of c-Src by abolishing the binding of SH2 with phosphorylated Tyr527.
Mentions: The activation and inhibition of Src involve PTPs which dephosphorylate tyrosine residues, significant for the regulation of these kinases. In addition, important in the regulation of Src activity are SH2 domains, which recognize phosphotyrosine residues and thus stabilize the inactive conformation of Src. The structure of Src contains two tyrosine residues that are key for the regulation of this family of kinases (Figure 4) [73,74]. In c-Src these are Tyr527 and Tyr416. After the phosphorylation of c-Src Tyr527, the SH2 domain of this protein binds to c-Src P-Tyr527, stabilizing the inactive conformation of c-Src. The activation of this kinase family consists in the dephosphorylation of P-Tyr527 by various PTPs [73]. After the dephosphorylation of c-Src Tyr527, this kinase is in the intermediate conformation, between the active and inactive conformation. Then cross-autophosphorylation occurs by another c-Src, at Tyr416, which induces a conformational change and the full activation of the enzyme [74,75]. c-Src inactivation involves PTP-induced dephosphorylation of residues of c-Src P-Tyr416 and phosphorylation of c-Src Tyr527 by different kinases [74]. After this modification the SH2 domain stabilizes the inactive conformation of c-Src.

Bottom Line: We refer mainly to the effects of vanadate (orthovanadate), vanadyl and pervanadate ions; the main focus is placed on their impact on intracellular signaling.We describe the exact mechanism of the effect of vanadium compounds on protein tyrosine phosphatases (PTP), epidermal growth factor receptor (EGFR), PLCγ, Src, mitogen-activated protein kinase (MAPK) cascades, transcription factor NF-κB, the effect on the proteolysis of COX-2 and the activity of cPLA2.For a better understanding of these processes, a lot of space is devoted to the transformation of vanadium compounds within the cell and the molecular influence on the direct targets of the discussed vanadium compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111 Szczecin, Poland. jan.korbecki@onet.eu.

ABSTRACT
This paper discusses how the activity and expression of cyclooxygenases are influenced by vanadium compounds at anticancer concentrations and recorded in inorganic vanadium poisonings. We refer mainly to the effects of vanadate (orthovanadate), vanadyl and pervanadate ions; the main focus is placed on their impact on intracellular signaling. We describe the exact mechanism of the effect of vanadium compounds on protein tyrosine phosphatases (PTP), epidermal growth factor receptor (EGFR), PLCγ, Src, mitogen-activated protein kinase (MAPK) cascades, transcription factor NF-κB, the effect on the proteolysis of COX-2 and the activity of cPLA2. For a better understanding of these processes, a lot of space is devoted to the transformation of vanadium compounds within the cell and the molecular influence on the direct targets of the discussed vanadium compounds.

No MeSH data available.


Related in: MedlinePlus