Tumor necrosis factor activates CRE-binding protein through a p38 MAPK/ MSK1 signaling pathway in endothelial cells

Jason A. Gustin, Roxana Pincheira, Lindsey Mayo, Osman Nidai Ozes, Kelly M. Kessler, Melinda R. Baerwald, Chandrashekhar K. Korgaonkar, David B. Donner

Research output: Contribution to journalArticle

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Abstract

Tumor necrosis factor (TNF) promotes immunity and modulates cell viability, in part, by promoting alterations of cellular gene expression. The mechanisms through which TNF communicates with the nucleus and alters gene expression are incompletely understood. Incubation of human umbilical vein endothelial cells (HUVEC) with TNF induces phosphorylation of the CRE-binding protein (CREB) transcription factor on serine 133 and increases CREB DNA binding and transactivation. Dominant negative CREB, an antagonist antibody directed against the type 1 TNF receptor, or pharmacological inhibition of p38 MAPK signaling blocked TNF-induced CREB activation as determined by phosphorylation and gene reporter assays. From among the kinases that can activate CREB, we found that downstream of p38 MAPK, MSK1 is activated by TNF to promote CREB activation. These observations show that CREB is activated by TNF/TNFR1 signaling through a p38 MAPK/MSK1 signaling pathway.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume286
Issue number3 55-3
StatePublished - Mar 2004

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Endothelial cells
p38 Mitogen-Activated Protein Kinases
Carrier Proteins
Endothelial Cells
Tumor Necrosis Factor-alpha
Receptors, Tumor Necrosis Factor, Type I
Phosphorylation
DNA-Binding Proteins
Gene expression
Chemical activation
Gene Expression
Human Umbilical Vein Endothelial Cells
Reporter Genes
Serine
Transcriptional Activation
Immunity
Assays
Cell Survival
Transcription Factors
Phosphotransferases

Keywords

  • Cyclic adenosine 5′-monophosphate response element

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Gustin, J. A., Pincheira, R., Mayo, L., Ozes, O. N., Kessler, K. M., Baerwald, M. R., ... Donner, D. B. (2004). Tumor necrosis factor activates CRE-binding protein through a p38 MAPK/ MSK1 signaling pathway in endothelial cells. American Journal of Physiology - Cell Physiology, 286(3 55-3).

Tumor necrosis factor activates CRE-binding protein through a p38 MAPK/ MSK1 signaling pathway in endothelial cells. / Gustin, Jason A.; Pincheira, Roxana; Mayo, Lindsey; Ozes, Osman Nidai; Kessler, Kelly M.; Baerwald, Melinda R.; Korgaonkar, Chandrashekhar K.; Donner, David B.

In: American Journal of Physiology - Cell Physiology, Vol. 286, No. 3 55-3, 03.2004.

Research output: Contribution to journalArticle

Gustin, JA, Pincheira, R, Mayo, L, Ozes, ON, Kessler, KM, Baerwald, MR, Korgaonkar, CK & Donner, DB 2004, 'Tumor necrosis factor activates CRE-binding protein through a p38 MAPK/ MSK1 signaling pathway in endothelial cells', American Journal of Physiology - Cell Physiology, vol. 286, no. 3 55-3.
Gustin, Jason A. ; Pincheira, Roxana ; Mayo, Lindsey ; Ozes, Osman Nidai ; Kessler, Kelly M. ; Baerwald, Melinda R. ; Korgaonkar, Chandrashekhar K. ; Donner, David B. / Tumor necrosis factor activates CRE-binding protein through a p38 MAPK/ MSK1 signaling pathway in endothelial cells. In: American Journal of Physiology - Cell Physiology. 2004 ; Vol. 286, No. 3 55-3.
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