What question did this study set out to answer?

To elucidate the coordinated phosphorylation and dephosphorylation mechanisms at Ser-1177 and Thr-495 regulating endothelial nitric-oxide synthase (eNOS) activity.

May 1, 2001Journal of Biological ChemistryOpen Access

Coordinated Control of Endothelial Nitric-oxide Synthase Phosphorylation by Protein Kinase C and the cAMP-dependent Protein Kinase

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To elucidate the coordinated phosphorylation and dephosphorylation mechanisms at Ser-1177 and Thr-495 regulating endothelial nitric-oxide synthase (eNOS) activity.
Examined Ser-1177 and Thr-495 phosphorylation dynamics in endothelial cells in response to VEGF, PKA, and PKC pathway stimulation.
Assessed the association and site-specificity of phosphatases PP1 and PP2A using synthetic phosphopeptides and selective inhibitors calyculin and okadaic acid.
PKC signaling inhibited eNOS by phosphorylating Thr-495 and dephosphorylating Ser-1177, whereas PKA activated eNOS through reciprocal Ser-1177 phosphorylation and Thr-495 dephosphorylation.
PP1 specifically mediated Thr-495 dephosphorylation (blocked by calyculin), while PP2A selectively dephosphorylated Ser-1177 (blocked by okadaic acid), explaining VEGF-induced transient phosphorylation shifts.

Structured PICO

Population

Endothelial cells

Intervention

VEGF signaling, PKC/PKA signaling, and treatment with calyculin or okadaic acid

Outcome

eNOS phosphorylation at Ser-1177 and Thr-495surrogate

This preclinical study demonstrates that eNOS activity is tightly regulated by coordinated phosphorylation and dephosphorylation at specific sites (Ser-1177 and Thr-495) involving multiple kinases and phosphatases.

Discussion

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Implication

eNOS site-specific regulation remains hypothesis-generating in animal models; leaves open targeted phosphatase modulation for endothelial dysfunction.

Cite This Study

Michell et al. (2001) studied this question.

synapsesocial.com/papers/6a6f2e4478a11c550e08dd10 https://doi.org/10.1074/jbc.c100122200

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Implication

eNOS site-specific regulation remains hypothesis-generating in animal models; leaves open targeted phosphatase modulation for endothelial dysfunction.

Coordinated Control of Endothelial Nitric-oxide Synthase Phosphorylation by Protein Kinase C and the cAMP-dependent Protein Kinase

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Coordinated Control of Endothelial Nitric-oxide Synthase Phosphorylation by Protein Kinase C and the cAMP-dependent Protein Kinase

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider