1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in human keratinocytes

Claus Johansen; Knud Kragballe; Jeanette Henningsen; Majken Westergaard; Karsten Kristiansen; Lars Iversen

doi:10.1046/j.1523-1747.2003.12095.x

1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in human keratinocytes

Claus Johansen, Knud Kragballe, Jeanette Henningsen, Majken Westergaard, Karsten Kristiansen, Lars Iversen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

57 Citationer (Scopus)

Abstract

Udgivelsesdato: 2003-Apr

Originalsprog	Engelsk
Tidsskrift	Journal of Investigative Dermatology
Vol/bind	120
Udgave nummer	4
Sider (fra-til)	561-70
Antal sider	9
ISSN	0022-202X
DOI	https://doi.org/10.1046/j.1523-1747.2003.12095.x
Status	Udgivet - 2003
Udgivet eksternt	Ja

Bibliografisk note

Keywords: 1-Phosphatidylinositol 3-Kinase; Adult; Annexin A2; Antibodies; Calcitriol; Calcium Channel Agonists; Cells, Cultured; Gene Expression; Humans; JNK Mitogen-Activated Protein Kinases; Keratinocytes; MAP Kinase Kinase Kinase 1; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Phosphorylation; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; RNA, Messenger; Transcription Factor AP-1; ras Proteins

Adgang til dokumentet

10.1046/j.1523-1747.2003.12095.x

Citationsformater

Johansen, C., Kragballe, K., Henningsen, J., Westergaard, M., Kristiansen, K., & Iversen, L. (2003). 1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in human keratinocytes. Journal of Investigative Dermatology, 120(4), 561-70. https://doi.org/10.1046/j.1523-1747.2003.12095.x

1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in human keratinocytes. / Johansen, Claus; Kragballe, Knud; Henningsen, Jeanette et al.
I: Journal of Investigative Dermatology, Bind 120, Nr. 4, 2003, s. 561-70.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Johansen, C, Kragballe, K, Henningsen, J, Westergaard, M, Kristiansen, K & Iversen, L 2003, '1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in human keratinocytes', Journal of Investigative Dermatology, bind 120, nr. 4, s. 561-70. https://doi.org/10.1046/j.1523-1747.2003.12095.x

Johansen C, Kragballe K, Henningsen J, Westergaard M, Kristiansen K, Iversen L. 1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in human keratinocytes. Journal of Investigative Dermatology. 2003;120(4):561-70. doi: 10.1046/j.1523-1747.2003.12095.x

Johansen, Claus ; Kragballe, Knud ; Henningsen, Jeanette et al. / 1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in human keratinocytes. I: Journal of Investigative Dermatology. 2003 ; Bind 120, Nr. 4. s. 561-70.

@article{b271cad00ef211de8478000ea68e967b,

title = "1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in human keratinocytes",

abstract = "1alpha,25-Dihydroxyvitamin D3 added to human keratinocytes increases differentiation through an activation of the transcription factor activator protein 1. We have previously reported that the 1alpha,25-dihydroxyvitamin D3-induced increase of activator protein 1 DNA binding activity is mediated by a protein kinase C-independent mechanism. The purpose of this study was to investigate further the mechanisms by which 1alpha,25-dihydroxyvitamin D3 modulates activator protein 1 DNA binding activity in cultured normal human keratinocytes. Western blotting experiments revealed that 1alpha,25-dihydroxyvitamin D3 caused a rapid and transient activation of the mitogen-activated protein kinases, extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1. 1alpha,25-Dihydroxyvitamin D3 also enhanced the expression of the activator protein 1 subunits, c-Fos, Fra1, and c-Jun as determined by northern and western blotting. The 1alpha,25-dihydroxyvitamin D3-induced activator protein 1 DNA binding activity was completely blocked by the MEK inhibitor PD 98059 indicating that the MEK/extracellular signal regulated kinase pathway is involved in the activation of activator protein 1. Transfection experiments showed that 1alpha,25-dihydroxyvitamin D3 also increased the activator protein 1-dependent transactivation, which was completely blocked by expression of a dominant negative Ras, suggesting that the 1alpha,25-dihydroxyvitamin D3-induced activator protein 1 activity involves Ras-dependent signaling. Furthermore, preincubation of the keratinocytes with the specific phosphatidylinositol 3-kinase inhibitors, Wortmannin and LY294002, demonstrated that the 1alpha,25-dihydroxyvitamin D3-induced activation of extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1 required phosphatidylinositol 3-kinase activity. Finally, preincubation of keratinocytes with a polyclonal antibody against the membrane receptor annexin II, blocked the 1alpha,25-dihydroxyvitamin D3-induced activation of extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1. Taken together, our results indicate that 1alpha,25-dihydroxyvitamin D3, via binding to the membrane receptor annexin II, induces activation of the phos-phatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1 signal transduction pathway resulting in increased expression of c-Fos, Fra1, and c-Jun, and subsequently increased activator protein 1 DNA binding activity and gene transcription.",

author = "Claus Johansen and Knud Kragballe and Jeanette Henningsen and Majken Westergaard and Karsten Kristiansen and Lars Iversen",

note = "Keywords: 1-Phosphatidylinositol 3-Kinase; Adult; Annexin A2; Antibodies; Calcitriol; Calcium Channel Agonists; Cells, Cultured; Gene Expression; Humans; JNK Mitogen-Activated Protein Kinases; Keratinocytes; MAP Kinase Kinase Kinase 1; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Phosphorylation; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; RNA, Messenger; Transcription Factor AP-1; ras Proteins",

year = "2003",

doi = "10.1046/j.1523-1747.2003.12095.x",

language = "English",

volume = "120",

pages = "561--70",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "nature publishing group",

number = "4",

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TY - JOUR

T1 - 1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in human keratinocytes

AU - Johansen, Claus

AU - Kragballe, Knud

AU - Henningsen, Jeanette

AU - Westergaard, Majken

AU - Kristiansen, Karsten

AU - Iversen, Lars

N1 - Keywords: 1-Phosphatidylinositol 3-Kinase; Adult; Annexin A2; Antibodies; Calcitriol; Calcium Channel Agonists; Cells, Cultured; Gene Expression; Humans; JNK Mitogen-Activated Protein Kinases; Keratinocytes; MAP Kinase Kinase Kinase 1; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Phosphorylation; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; RNA, Messenger; Transcription Factor AP-1; ras Proteins

PY - 2003

Y1 - 2003

N2 - 1alpha,25-Dihydroxyvitamin D3 added to human keratinocytes increases differentiation through an activation of the transcription factor activator protein 1. We have previously reported that the 1alpha,25-dihydroxyvitamin D3-induced increase of activator protein 1 DNA binding activity is mediated by a protein kinase C-independent mechanism. The purpose of this study was to investigate further the mechanisms by which 1alpha,25-dihydroxyvitamin D3 modulates activator protein 1 DNA binding activity in cultured normal human keratinocytes. Western blotting experiments revealed that 1alpha,25-dihydroxyvitamin D3 caused a rapid and transient activation of the mitogen-activated protein kinases, extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1. 1alpha,25-Dihydroxyvitamin D3 also enhanced the expression of the activator protein 1 subunits, c-Fos, Fra1, and c-Jun as determined by northern and western blotting. The 1alpha,25-dihydroxyvitamin D3-induced activator protein 1 DNA binding activity was completely blocked by the MEK inhibitor PD 98059 indicating that the MEK/extracellular signal regulated kinase pathway is involved in the activation of activator protein 1. Transfection experiments showed that 1alpha,25-dihydroxyvitamin D3 also increased the activator protein 1-dependent transactivation, which was completely blocked by expression of a dominant negative Ras, suggesting that the 1alpha,25-dihydroxyvitamin D3-induced activator protein 1 activity involves Ras-dependent signaling. Furthermore, preincubation of the keratinocytes with the specific phosphatidylinositol 3-kinase inhibitors, Wortmannin and LY294002, demonstrated that the 1alpha,25-dihydroxyvitamin D3-induced activation of extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1 required phosphatidylinositol 3-kinase activity. Finally, preincubation of keratinocytes with a polyclonal antibody against the membrane receptor annexin II, blocked the 1alpha,25-dihydroxyvitamin D3-induced activation of extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1. Taken together, our results indicate that 1alpha,25-dihydroxyvitamin D3, via binding to the membrane receptor annexin II, induces activation of the phos-phatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1 signal transduction pathway resulting in increased expression of c-Fos, Fra1, and c-Jun, and subsequently increased activator protein 1 DNA binding activity and gene transcription.

AB - 1alpha,25-Dihydroxyvitamin D3 added to human keratinocytes increases differentiation through an activation of the transcription factor activator protein 1. We have previously reported that the 1alpha,25-dihydroxyvitamin D3-induced increase of activator protein 1 DNA binding activity is mediated by a protein kinase C-independent mechanism. The purpose of this study was to investigate further the mechanisms by which 1alpha,25-dihydroxyvitamin D3 modulates activator protein 1 DNA binding activity in cultured normal human keratinocytes. Western blotting experiments revealed that 1alpha,25-dihydroxyvitamin D3 caused a rapid and transient activation of the mitogen-activated protein kinases, extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1. 1alpha,25-Dihydroxyvitamin D3 also enhanced the expression of the activator protein 1 subunits, c-Fos, Fra1, and c-Jun as determined by northern and western blotting. The 1alpha,25-dihydroxyvitamin D3-induced activator protein 1 DNA binding activity was completely blocked by the MEK inhibitor PD 98059 indicating that the MEK/extracellular signal regulated kinase pathway is involved in the activation of activator protein 1. Transfection experiments showed that 1alpha,25-dihydroxyvitamin D3 also increased the activator protein 1-dependent transactivation, which was completely blocked by expression of a dominant negative Ras, suggesting that the 1alpha,25-dihydroxyvitamin D3-induced activator protein 1 activity involves Ras-dependent signaling. Furthermore, preincubation of the keratinocytes with the specific phosphatidylinositol 3-kinase inhibitors, Wortmannin and LY294002, demonstrated that the 1alpha,25-dihydroxyvitamin D3-induced activation of extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1 required phosphatidylinositol 3-kinase activity. Finally, preincubation of keratinocytes with a polyclonal antibody against the membrane receptor annexin II, blocked the 1alpha,25-dihydroxyvitamin D3-induced activation of extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1. Taken together, our results indicate that 1alpha,25-dihydroxyvitamin D3, via binding to the membrane receptor annexin II, induces activation of the phos-phatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1 signal transduction pathway resulting in increased expression of c-Fos, Fra1, and c-Jun, and subsequently increased activator protein 1 DNA binding activity and gene transcription.

U2 - 10.1046/j.1523-1747.2003.12095.x

DO - 10.1046/j.1523-1747.2003.12095.x

M3 - Journal article

C2 - 12648218

SN - 0022-202X

VL - 120

SP - 561

EP - 570

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 4

ER -