Peroxynitrite activates kinases of the src family and upregulates tyrosine phosphorylation signaling.
The hypothesis that peroxynitrite may act as a signaling molecule able to upregulate protein tyrosine phosphorylation is discussed. This article focuses on the mechanisms for activating kinases of the src family, an important class of nonreceptor tyrosine kinases implicated in the regulation of cell communication, proliferation, migration, differentiation, and survival. Recent in vitro findings show that in erythrocytes, synaptosomes, and cerebellar primary culture cells peroxynitrite is able to inhibit phosphatases and to activate different members of the src kinase family through different mechanisms involving cysteine-dependent and -independent processes. The ability of nitrotyrosine-containing peptides with SH2 binding affinity to activate src kinases is also discussed.
Department of Cell Biology, Istituto Superiore di Sanità, Roma, Italy. mminetti@iss.it
Maurizio
M
Minetti
Cinzia
C
Mallozzi
A M Michela
AM
Di Stasi
D000818:Animals; D003545:Cysteine / Q000378:metabolism; D004058:Diffusion; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051572:Proto-Oncogene Proteins c-hck; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*; D015854:Up-Regulation; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism*
D005609:Free Radicals; D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D003545:Cysteine