Quantitative Phosphoproteomics Identifies Filaggrin and other Targets of Ionizing Radiation in a Human Skin Model

Journal Article · Tue Apr 17 00:00:00 EDT 2012 · Experimental Dermatology, 21(5):352–357

DOI:https://doi.org/10.1111/j.1600-0625.2012.01470.x· OSTI ID:1039123

Yang, Feng; Waters, Katrina M; Webb-Robertson, Bobbie-Jo M; Sowa, Marianne B; Freiin von Neubeck, Claere H; Aldrich, Joshua T; Markillie, Lye Meng; Wirgau, Rachel M; Gristenko, Marina A; Zhao, Rui; Camp, David G; Smith, Richard D; Stenoien, David L

Our objective here was to perform a quantitative phosphoproteomic study on a reconstituted human skin tissue to identify low and high dose ionizing radiation dependent signaling in a complex 3-dimensional setting. Application of an isobaric labeling strategy using sham and 3 radiation doses (3, 10, 200 cGy) resulted in the identification of 1113 unique phosphopeptides. Statistical analyses identified 151 phosphopeptides showing significant changes in response to radiation and radiation dose. Proteins responsible for maintaining skin structural integrity including keratins and desmosomal proteins (desmoglein, desmoplakin, plakophilin 1 and 2,) had altered phosphorylation levels following exposure to both low and high doses of radiation. A phosphorylation site present in multiple copies in the linker regions of human profilaggrin underwent the largest fold change. Increased phosphorylation of these sites coincided with altered profilaggrin processing suggesting a role for linker phosphorylation in human profilaggrin regulation. These studies demonstrate that the reconstituted human skin system undergoes a coordinated response to ionizing radiation involving multiple layers of the stratified epithelium that serve to maintain skin barrier functions and minimize the damaging consequences of radiation exposure.

• Research Organization: Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1039123
• Report Number(s): PNNL-SA-79030; EXDEEY; 40072; KP1602020; TRN: US201209%%186
• Journal Information: Experimental Dermatology, 21(5):352–357, Vol. 21, Issue 5; ISSN 0906-6705
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
EPITHELIUM
IONIZING RADIATIONS
KERATIN
LOW DOSE IRRADIATION
PHOSPHORYLATION
PEPTIDES
PROTEINS
RADIATION DOSES
SKIN
Environmental Molecular Sciences Laboratory