Regulation of protein kinase D during differentiation and proliferation of primary mouse keratinocytes

M. Ernest Dodd, Vladimir L. Ristich, Sagarika Ray, Robert M. Lober, Wendy B Bollag

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)294-306
Number of pages13
JournalJournal of Investigative Dermatology
Volume125
Issue number2
DOIs
StatePublished - Jan 1 2005

Fingerprint

Keratinocytes
Tetradecanoylphorbol Acetate
Acetates
protein kinase D
Keratin-5
Protein-Serine-Threonine Kinases
Mitogens
Skin Diseases
Epidermis
Serine
Skin
Chemical activation
Calcium
Recovery

Keywords

  • 12-O-tetradecanoylphorbol-13-acetate
  • Calcium
  • Protein kinase C
  • Skin
  • Tumorigenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Regulation of protein kinase D during differentiation and proliferation of primary mouse keratinocytes. / Dodd, M. Ernest; Ristich, Vladimir L.; Ray, Sagarika; Lober, Robert M.; Bollag, Wendy B.

In: Journal of Investigative Dermatology, Vol. 125, No. 2, 01.01.2005, p. 294-306.

Research output: Contribution to journalArticle

Dodd, M. Ernest ; Ristich, Vladimir L. ; Ray, Sagarika ; Lober, Robert M. ; Bollag, Wendy B. / Regulation of protein kinase D during differentiation and proliferation of primary mouse keratinocytes. In: Journal of Investigative Dermatology. 2005 ; Vol. 125, No. 2. pp. 294-306.
@article{25eeef245de548478030a3952a79c39b,
title = "Regulation of protein kinase D during differentiation and proliferation of primary mouse keratinocytes",
abstract = "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.",
keywords = "12-O-tetradecanoylphorbol-13-acetate, Calcium, Protein kinase C, Skin, Tumorigenesis",
author = "Dodd, {M. Ernest} and Ristich, {Vladimir L.} and Sagarika Ray and Lober, {Robert M.} and Bollag, {Wendy B}",
year = "2005",
month = "1",
day = "1",
doi = "10.1111/j.0022-202X.2005.23780.x",
language = "English (US)",
volume = "125",
pages = "294--306",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "2",

}

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

PY - 2005/1/1

Y1 - 2005/1/1

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

UR - http://www.scopus.com/inward/record.url?scp=24344451280&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24344451280&partnerID=8YFLogxK

U2 - 10.1111/j.0022-202X.2005.23780.x

DO - 10.1111/j.0022-202X.2005.23780.x

M3 - Article

VL - 125

SP - 294

EP - 306

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 2

ER -