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S‐NITROSYLATION OF PROTEIN TYROSINE PHOSPHATASE IN ENDOTHELIAL CELLS UNDER FLOW
Author(s) -
Wang Ling Danny
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a624-d
Subject(s) - s nitrosylation , protein tyrosine phosphatase , nitric oxide , chemistry , enos , phosphatase , microbiology and biotechnology , nitrosylation , biochemistry , nadph oxidase , intracellular , nitric oxide synthase , tyrosine , phosphorylation , reactive oxygen species , biology , enzyme , cysteine , organic chemistry
Vascular endothelial cells (ECs) are constantly exposed to blood flow‐induced shear stress. This shear flow increases the expression of endothelial nitric oxide synthase (eNOS), as well as its activity to produce nitric oxide (NO). Recent study suggests that NO similar to H 2 O 2 , as a second messenger to regulate signaling through S‐nitrosylation of catalytic Cys residue in protein tyrosine phosphatases (PTPs). Present study is studying the S‐nitorsylation of PTP in ECs under flow. Src homolog‐2 domain‐containing protein tyrosine phosphatase (SHP2) is an important PTP participating in various signaling pathways. ECs exposed to laminar flow as well as to SNAP (NO donor) pretreatment, lead to a transient inhibition of SHP2 activities mediated by S‐nitrosylation of SHP2. L‐NAME (eNOS inhibitor) pretreatment of ECs exposed to flow, significantly reduced this S‐nitrosylation of SHP2. In contrast, ECs treating with am inhibitor to NADPH oxidase (DPI) to decrease intracellular ROS level were shown to have an increased S‐nitrosylation of SHP2. Consistently, ECs exposed to H 2 O 2 increased the oxidative modification of SHP2 concurrently with a decrease of S‐nitrosylation of SHP2. Utilizing biotin switch method, ECs over‐expressed SHP2 mutant (SHP2 C459S ) abolished the S‐nitrosylation in SHP2 as compared to those wild type controls. This result indicates SHP2 is predominantly S‐nitrosylated at catalytic Cys‐459 in ECs under laminar flow. Our results suggest that H 2 O 2 and NO compete to react to catalytic Cys residue in PTP. S‐nitrosylation of catalytic Cys residue in PTP may protect it from H 2 O 2 ‐induced irreversible oxidation. The reversible S‐nitrosylation of PTP may play an important role in regulating endothelial responses to various stimuli under flow condition.