UVA inactivates protein tyrosine phosphatases by calpain-mediated degradation.
UV irradiation causes inflammatory and proliferative cellular responses. We have proposed previously that these effects are, to a large extent, caused by the ligand-independent activation of several receptor tyrosine kinases due to the inactivation of their negative control elements, the protein tyrosine phosphatases (PTPs). We examined the mechanism of this inactivation and found that, in addition to reversible oxidation of PTPs, UV triggers a novel mechanism: induced degradation of PTPs by calpain, which requires both calpain activation and substrate PTP oxidative modification. This as yet unrecognized effect of UV is irreversible, occurs predominantly with UVA and UVB, the range of wavelengths in sunlight that reach the skin surface, and at physiologically relevant doses.
Gulati
Pawan
P
Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, Herrmann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
Markova
Boyka
B
Göttlicher
Martin
M
Böhmer
Frank-D
FD
Herrlich
Peter A
PA
D002154:Calpain / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000528:radiation effects*; D004789:Enzyme Activation; D006801:Humans; D010084:Oxidation-Reduction; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D014466:Ultraviolet Rays
D017027:Protein Tyrosine Phosphatases; D002154:Calpain