Activation of Protein Phosphorylation by Oxidants in Vascular Endothelial Cells: Identification of Tyrosine Phosphorylation of Caveolin

Vepa, Suryanarayana; Scribner, William M.; Natarajan, Viswanathan

doi:10.1016/s0891-5849(96)00241-9

Cited by 65 publications

(49 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1), which is similar to the results of previous studies performed in bovine pulmonary artery endothelial cells and placenta artery endothelial cells [28][29][30]. We found that catalase and NAC were able to suppress H 2 O 2 -induced caveolin-1 phosphorylation; however, the effect of NAC was modest compared to catalase.…”

Section: Discussionsupporting

confidence: 91%

“…Previous studies demonstrated that H 2 O 2 induces the phosphorylation of caveolin-1 at Tyr 14 in bovine pulmonary artery endothelial cells and placenta artery endothelial cells [28][29][30]. To determine whether H 2 O 2 induces the phosphorylation of caveolin-1 in brain astrocytes, rat primary astrocytes, human astroglioma cells (CRT-MG, U87-MG, and U251-MG) and HUVECs were treated with 1 mM H 2 O 2 for 10 min and examined by immunoblotting for p-caveolin-1.…”

Section: H 2 O 2 Induces Caveolin-1 Phosphorylation At Tyr 14 In Braimentioning

confidence: 98%

See 1 more Smart Citation

SHP-2 Binds to Caveolin-1 and Regulates Src Activity via Competitive Inhibition of Csk in Response to H2O2 in Astrocytes

Lee

Kang

et al. 2012

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Reactive oxygen species (ROS) regulate diverse cellular functions by triggering signal transduction events, such as Src and mitogen-activated protein (MAP) kinases. Here, we report the role of caveolin-1 and Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) in H 2 O 2 -induced signaling pathway in brain astrocytes. H 2 O 2 -mediated oxidative stress induced phosphorylation of caveolin-1 and association between p-caveolin-1 and SHP-2. SHP-2 specifically bound to wild-type caveolin-1 similarly to c-Src tyrosine kinase (CSK), but not to phosphorylation-deficient mutant of caveolin-1 (Y14A), and interfered with complex formation between caveolin-1 and CSK. In the presence of CSK siRNA, binding between caveolin-1 and SHP-2 was enhanced by H 2 O 2 treatment, which led to reduced Src phosphorylation at tyrosine (Tyr) 530 and enhanced Src phosphorylation at Tyr 419. In contrast, siRNA targeting of SHP-2 facilitated H 2 O 2 -mediated interaction between caveolin-1 and CSK and enhanced Src phosphorylation at Tyr 530, leading to subsequent decrease in Src downstream signaling, such as focal adhesion kinase (FAK) and extracellular signal-related kinase (ERK). Our results collectively indicate that SHP-2 alters Src kinase activity by interfering with the complex formation between CSK and phosphotyrosine caveolin-1 in the presence of H 2 O 2 , thus functions as a positive regulator in Src signaling under oxidative stress in brain astrocytes.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: H 2 O 2 Induces Caveolin-1 Phosphorylation At Tyr 14 In Braimentioning

confidence: 98%

SHP-2 Binds to Caveolin-1 and Regulates Src Activity via Competitive Inhibition of Csk in Response to H2O2 in Astrocytes

Lee

Kang

et al. 2012

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…However, the nature of tyrosine phosphorylated proteins involved in PLD activation has not been identified. Earlier studies by Vepa et al (24) indicate that caveolin and FAK (125 kDa) are targets for H202 in ECs. In this study, we have identified ERK-1 and ERK-2 and focal adhesion proteins (FAK and paxillin) as potential targets for ROS-induced tyrosine phosphorylation.…”

Section: Discussionmentioning

confidence: 92%

Reactive oxygen species signaling through regulation of protein tyrosine phosphorylation in endothelial cells.

Natarajan

Scribner

Al-Hassani

et al. 1998

Environ Health Perspect

View full text Add to dashboard Cite

Tyrosine phosphorylation of proteins, controlled by tyrosine kinases and protein tyrosine phosphatases, plays a key role in cellular growth and differentiating. A wide variety of hormones, growth factors, and cytokines modulate cellular tyrosine phosphorylation to transmit signals across the plasma membrane to the nucleus. Recent studies suggest that reactive oxygen species (ROS) also induce cellular protein tyrosine phosphorylation through receptor or nonreceptor tyrosine kinases. To determine whether protein tyrosine phosphorylation by ROS regulates endothelial cell (EC) metabolism and function, we exposed vascular ECs to H202 or H202 plus vanadate. This resulted in a time-and dose-dependent increase in protein tyrosine phosphorylation of several proteins (Mr 21-200 kDa), as determined by immunoprecipitation and Western blot analysis with antiphosphotyrosine antibody. Immunoprecipitation with specific antibodies identified increased tyrosine phosphorylation of mitogen-activated protein kinases (42-44 kDa), paxillin (68 kDa), and FAK (125 kDa) by ROS. An immediate signaling response to increased protein tyrosine phosphorylation by ROS was activation of phospholipases such as A2, C, and D. Suramin pretreatment inhibited ROS stimulation of phospholipase D (PLD), suggesting a role for growth factor receptors in this activation. Further, PLD activation by ROS was attenuated by Nacetylcysteine, indicating that intracellular thiol status is critical to ROS-mediated signal transduction. These results provide evidence that ROS modulate EC signal transduction via a protein tyrosine phosphorylation-dependent mechanism.

show abstract

“…23,74 However, the role of this posttranslational modification in endothelial cell function remains to be established.…”

Section: Discussionmentioning

confidence: 99%

Caveolin, Caveolae, and Endothelial Cell Function

Frank

Woodman

Park

et al. 2003

ATVB

333

255

View full text Add to dashboard Cite

Abstract-Caveolae are 50-to 100-nm cell-surface plasma membrane invaginations observed in terminally differentiated cells. They are particularly abundant in endothelial cells, where they are believed to play a major role in the regulation of endothelial vesicular trafficking and signal transduction. The use of caveolin-1-deficient mice has provided many new insights into the roles of caveolae and caveolin-1 in the regulation of endothelial cell function. These novel findings suggest an important role for caveolin-1 in the pathogenesis of cancer, atherosclerosis, and vascular disease.

show abstract

Activation of Protein Phosphorylation by Oxidants in Vascular Endothelial Cells: Identification of Tyrosine Phosphorylation of Caveolin

Cited by 65 publications

References 34 publications

SHP-2 Binds to Caveolin-1 and Regulates Src Activity via Competitive Inhibition of Csk in Response to H2O2 in Astrocytes

SHP-2 Binds to Caveolin-1 and Regulates Src Activity via Competitive Inhibition of Csk in Response to H2O2 in Astrocytes

Reactive oxygen species signaling through regulation of protein tyrosine phosphorylation in endothelial cells.

Caveolin, Caveolae, and Endothelial Cell Function

Contact Info

Product

Resources

About