TY - JOUR
T1 - Regulation of protein kinase D during differentiation and proliferation of primary mouse keratinocytes
AU - Dodd, M. Ernest
AU - Ristich, Vladimir L.
AU - Ray, Sagarika
AU - Lober, Robert M.
AU - Bollag, Wendy B.
N1 - Funding Information:
We thank David Hardy, Xiaofeng Zhong, and Peter Parker for excellent technical assistance and Brian Shapiro and Xiangjian Zheng for scientific discussions. We thank Dr Bogi Andersen for kindly providing the keratin 5–luciferase construct and Dr Daniel Bikle for kindly providing the involucrin–luciferase construct. We thank Dr Maurice Pechet for the generous gift of 1,25(OH)D. We thank Joyce Wilson for preparing the frozen epidermal sections used for immunohistochemistry. This work was presented in part at the 36th and 37th Annual Southeast Regional Lipid Conferences and the International Investigative Dermatology 2003 meeting in Miami Beach, Florida and was submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (MED). This work was supported by National Institutes of Health Grant AR45212 and a Combined Intramural Grant Program award from the Medical College of Georgia Research Institute.
PY - 2005/8
Y1 - 2005/8
N2 - Diseased skin often exhibits a deregulated program of the keratinocyte maturation necessary for epidermal stratification and function. Protein kinase D (PKD), a serine/threonine kinase, is expressed in proliferating keratinocytes, and PKD activation occurs in response to mitogen stimulation in other cell types. We have proposed that PKD functions as a pro-proliferative and/or anti-differentiative signal in keratinocytes and hypothesized that differentiation inducers will downmodulate PKD to allow differentiation to proceed. Thus, changes in PKD levels, autophosphorylation, and activity were analyzed upon stimulation of differentiation and proliferation in primary mouse keratinocytes. Elevated extracellular calcium and acute 12-O- tetradecanoylphorbol-13-acetate (TPA) treatments induced differentiation and triggered a downmodulation of PKD levels, autophosphorylation at serine 916, and activity. Chronic TPA treatment stimulated proliferation and resulted in a recovery of PKD levels, autophosphorylation, and activity. Immunohistochemical analysis demonstrated PKD localization predominantly in the proliferative basal layer of mouse epidermis. Co-expression studies revealed a pro-proliferative, anti-differentiative effect of PKD on keratinocyte maturation as monitored by increased and decreased promoter activities of keratin 5, a proliferative marker, and involucrin, a differentiative marker, respectively. This work describes the inverse regulation of PKD during keratinocyte differentiation and proliferation and the pro-proliferative/anti-differentiative effects of PKD co-expression on keratinocyte maturation.
AB - Diseased skin often exhibits a deregulated program of the keratinocyte maturation necessary for epidermal stratification and function. Protein kinase D (PKD), a serine/threonine kinase, is expressed in proliferating keratinocytes, and PKD activation occurs in response to mitogen stimulation in other cell types. We have proposed that PKD functions as a pro-proliferative and/or anti-differentiative signal in keratinocytes and hypothesized that differentiation inducers will downmodulate PKD to allow differentiation to proceed. Thus, changes in PKD levels, autophosphorylation, and activity were analyzed upon stimulation of differentiation and proliferation in primary mouse keratinocytes. Elevated extracellular calcium and acute 12-O- tetradecanoylphorbol-13-acetate (TPA) treatments induced differentiation and triggered a downmodulation of PKD levels, autophosphorylation at serine 916, and activity. Chronic TPA treatment stimulated proliferation and resulted in a recovery of PKD levels, autophosphorylation, and activity. Immunohistochemical analysis demonstrated PKD localization predominantly in the proliferative basal layer of mouse epidermis. Co-expression studies revealed a pro-proliferative, anti-differentiative effect of PKD on keratinocyte maturation as monitored by increased and decreased promoter activities of keratin 5, a proliferative marker, and involucrin, a differentiative marker, respectively. This work describes the inverse regulation of PKD during keratinocyte differentiation and proliferation and the pro-proliferative/anti-differentiative effects of PKD co-expression on keratinocyte maturation.
KW - 12-O-tetradecanoylphorbol-13-acetate
KW - Calcium
KW - Protein kinase C
KW - Skin
KW - Tumorigenesis
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U2 - 10.1111/j.0022-202X.2005.23780.x
DO - 10.1111/j.0022-202X.2005.23780.x
M3 - Article
C2 - 16098040
AN - SCOPUS:24344451280
SN - 0022-202X
VL - 125
SP - 294
EP - 306
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 2
ER -