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Nitration of PECAM-1 ITIM tyrosines abrogates phosphorylation and SHP-2 binding. Biochem Biophys Res Commun 2002 Sep 06;296(5):1171-9

Date

09/05/2002

Pubmed ID

12207897

DOI

10.1016/s0006-291x(02)02060-0

Scopus ID

2-s2.0-0036392047 (requires institutional sign-in at Scopus site)   36 Citations

Abstract

Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is a cell adhesion molecule with a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) that, when phosphorylated, binds Src homology 2 domain-containing protein-tyrosine phosphatase (SHP-2). PECAM-1 is expressed at endothelial cell junctions where exposure to inflammatory intermediates may result in post-translational amino acid modifications that affect protein structure and function. Reactive nitrogen species (RNS), which are produced at sites of inflammation, nitrate tyrosine residues, and several proteins modified by tyrosine nitration have been found in diseased tissue. We show here that the RNS, peroxynitrite, induced nitration of both full-length cellular PECAM-1 and a purified recombinant PECAM-1 cytoplasmic domain. Mass spectrometric analysis of tryptic fragments revealed quantitative nitration of ITIM tyrosine 686. A synthetic peptide containing 3-nitrotyrosine at position 686 could not be phosphorylated nor bind SHP-2. These data suggest that ITIM tyrosine nitration may represent a mechanism for modulating phosphotyrosine-dependent signal transduction pathways.

Author List

Newman DK, Hoffman S, Kotamraju S, Zhao T, Wakim B, Kalyanaraman B, Newman PJ

Authors

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin
Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin
Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Cell Line
Humans
Intracellular Signaling Peptides and Proteins
Jurkat Cells
Molecular Sequence Data
Peroxynitrous Acid
Phosphorylation
Phosphotyrosine
Platelet Endothelial Cell Adhesion Molecule-1
Protein Binding
Protein Structure, Tertiary
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatases
Receptors, Immunologic
Tyrosine