Study of the regulation of eNOS Tyr81 phosphorylation

• Grant number: 18/10414-0
• Support type: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): September 01, 2018
• Effective date (End): August 31, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal researcher: Gilberto de Nucci
• Grantee: Alberto Fernando Oliveira Justo
• Supervisor abroad: Ingrid Fleming
• Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: Goethe University Frankfurt, Germany
• Associated to the scholarship: 16/09539-8 - Pharmacological, eletrophysiological and morphological characterization of a novel tetrodotoxin-resistant sodium channel coupled to corpus cavernosum of snakes, BP.DD

Abstract

The phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) on Tyr81 was shown to increase NO production and blood vessel relaxation in response to agonist stimulation. Although Src has been initially reported to phosphorylate this tyrosine residue, the regulation of the phosphorylation of this site remains largely unexplored. Preliminary work at the Institute for Vascular Signaling demonstrated that the tyrosine protein kinase ABL1 and the vascular endothelial protein tyrosine phosphatase (VE-PTP) modulate the phosphorylation of eNOS on Tyr81 in human endothelial cells in vitro. Further studies will establish the relevance of these findings for the modulation of NO-dependent vascular responses in intact vessels. In addition, as ABL1, VE-PTP and eNOS have been shown to play a role in the modulation of endothelial barrier integrity, the effects of the inhibition of ABL1 and VE-PTP on vascular permeability will be determined. (AU)