Protein Kinase C β2-Dependent Phosphorylation of Core 2 GlcNAc-T Promotes Leukocyte-Endothelial Cell Adhesion
| العنوان: | Protein Kinase C β2-Dependent Phosphorylation of Core 2 GlcNAc-T Promotes Leukocyte-Endothelial Cell Adhesion |
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| المؤلفون: | Eva M. Kohner, Retinopathy Chibber, Bahaedin M. Ben-Mahmud, Giovanni E. Mann, Jin J. Zhang |
| المصدر: | Diabetes. 52:1519-1527 |
| بيانات النشر: | American Diabetes Association, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | U937 cell, Endocrinology, Diabetes and Metabolism, Adhesion, Biology, medicine.disease, Cell biology, Serine, Endothelial stem cell, Biochemistry, Internal Medicine, medicine, Phosphorylation, Cell adhesion, Protein kinase C, Retinopathy |
| الوصف: | Increased leukocyte-endothelial cell adhesion is a key early event in the development of retinopathy and atherogenesis in diabetic patients. We recently reported that raised activity of glycosylating enzyme [β]1,6 acetylglucosaminyltransferase (core 2 GlcNAc-T) is responsible for increased leukocyte-endothelial cell adhesion and capillary occlusion in retinopathy. Here, we demonstrate that elevated glucose increases the activity of core 2 GlcNAc-T and adhesion of human leukocytes to retinal capillary endothelial cells, in a dose-dependent manner, through diabetes-activated serine/threonine protein kinase C β2 (PKCβ2)-dependent phosphorylation. This regulatory mechanism, involving phosphorylation of core 2 GlcNAc-T, is also present in polymorphonuclear leukocytes isolated from type 1 and type 2 diabetic patients. Inhibition of PKCβ2 activation with the specific inhibitor, LY379196, attenuated serine phosphorylation of core 2 GlcNAc-T and prevented increased leukocyte-endothelial cell adhesion. Raised activity of core 2 GlcNAc-T was associated with a threefold increase in O-linked glycosylation of P-selectin glycoprotein ligand-1 on the surface of leukocytes of diabetic patients compared with age-matched control subjects. PKCβ2-dependent phosphorylation of core 2 GlcNAc-T may thus represent a novel regulatory mechanism for activation of this key enzyme in mediating increased leukocyte-endothelial cell adhesion and capillary occlusion in diabetic retinopathy. |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::a3e6d1184730ea32b2b189e8e60cc0b9Test https://doi.org/10.2337/diabetes.52.6.1519Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........a3e6d1184730ea32b2b189e8e60cc0b9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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