کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3216957 1203587 2017 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PKC-δ and -η, MEKK-1, MEK-6, MEK-3, and p38-δ Are Essential Mediators of the Response of Normal Human Epidermal Keratinocytes to Differentiating Agents
ترجمه فارسی عنوان
PKC-δ و -η, MEKK-1, MEK-6, MEK-3, و p38-δ واسطه ‌های ضروری پاسخ طبیعی اپیدرمال کراتینوسیت انسانی برای عوامل افتراقی هستند
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
چکیده انگلیسی

Previous studies suggest that the novel protein kinase C (PKC) isoforms initiate a mitogen-activated protein kinase (MAPK) signaling cascade that regulates keratinocyte differentiation. However, assigning these functions has relied on treatment with pharmacologic inhibitors and/or manipulating kinase function using overexpression of wild-type or dominant-negative kinases. As these methods are not highly specific, an obligatory regulatory role for individual kinases has not been assigned. In this study, we use small interfering RNA knockdown to study the role of individual PKC isoforms as regulators of keratinocyte differentiation induced by the potent differentiating stimulus, 12-O-tetradecanoylphorbol-13-acetate (TPA). PKC-δ knockdown reduces TPA-activated involucrin promoter activity, nuclear activator protein-1 factor accumulation and binding to DNA, and cell morphology change. Knockdown of PKC downstream targets, including MEKK-1, MEK-6, MEK-3, or p38-δ, indicates that these kinases are required for these responses. Additional studies indicate that knockdown of PKC-η inhibits TPA-dependent involucrin promoter activation. In contrast, knockdown of PKC-α (a classical PKC isoform) or PKC-ε (a novel isoform) does not inhibit these TPA-dependent responses. Further studies indicate that PKC-δ is required for calcium and green tea polyphenol-dependent regulation of end responses. These findings are informative as they suggest an essential role for selected PKC and MAPK cascade enzymes in mediating a range of end responses to a range of differentiation stimuli in keratinocytes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 130, Issue 8, August 2010, Pages 2017–2030
نویسندگان
, , , ,