Oxidative inhibition of receptor-type protein-tyrosine phosphatase kappa by ultraviolet irradiation activates epidermal growth factor receptor in human keratinocytes.
Ultraviolet (UV) irradiation rapidly increases tyrosine phosphorylation (i.e. activates) of epidermal growth factor receptors (EGFR) in human skin. EGFR-dependent signaling pathways drive increased expression of matrix metalloproteinases, whose actions fragment collagen and elastin fibers, the primary structural protein components in skin connective tissue. Connective tissue fragmentation, which results from chronic exposure to solar UV irradiation, is a major determinant of premature skin aging (photoaging). UV irradiation generates reactive oxygen species, which readily react with conserved cysteine residues in the active site of protein-tyrosine phosphatases (PTP). We report here that EGFR activation by UV irradiation results from oxidative inhibition of receptor type PTP-kappa (RPTP-kappa). RPTP-kappa directly counters intrinsic EGFR tyrosine kinase activity, thereby maintaining EGFR in an inactive state. Reversible, oxidative inactivation of RPTP-kappa activity by UV irradiation shifts the kinase-phosphatase balance in favor of EGFR activation. These data delineate a novel mechanism of EGFR regulation and identify RPTP-kappa as a key molecular target for antioxidant protection against skin aging.
Xu
Yiru
Y
Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Shao
Yuan
Y
Voorhees
John J
JJ
Fisher
Gary J
GJ
D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D066246:ErbB Receptors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000378:metabolism; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D012867:Skin / Q000473:pathology* / Q000528:radiation effects; D014443:Tyrosine / Q000737:chemistry; D014466:Ultraviolet Rays
D014443:Tyrosine; D066246:ErbB Receptors; C489852:PTPRK protein, human; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D010100:Oxygen