The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates adipogenesis

Robert L. Kortum, Diane L. Costanzo, Jamie Haferbier, Steven J. Schreiner, Gina Razidlo, Ming Hoi Wu, Deanna J. Volle, Toshiyuki Mori, Hiroshi Sakaue, Nina V. Chaika, Oleg V. Chaika, Robert E. Lewis

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Mitogen-activated protein kinase pathways are implicated in the regulation of cell differentiation, although their precise roles in many differentiation programs remain elusive. The Raf/MEK/extracellular signal-regulated kinase (ERK) kinase cascade has been proposed to both promote and inhibit adipogenesis. Here, we titrate expression of the molecular scaffold kinase suppressor of Ras 1 (KSR1) to regulate signaling through the Raf/MEK/ERK/p90 ribosomal S6 kinase (RSK) kinase cascade and show how it determines adipogenic potential. Deletion of KSR1 prevents adipogenesis in vitro, which can be rescued by introduction of low levels of KSR1. Appropriate levels of KSR1 coordinate ERK and RSK activation with C/EBPβ synthesis leading to the phosphorylation and stabilization of C/EBPβ at the precise moment it is required within the adipogenic program. Elevated levels of KSR1 expression, previously shown to enhance cell proliferation, promote high, sustained ERK activation that phosphorylates and inhibits peroxisome proliferator-activated receptor gamma, inhibiting adipogenesis. Titration of KSR1 expression reveals how a molecular scaffold can modulate the intensity and duration of signaling emanating from a single pathway to dictate cell fate.

Original languageEnglish (US)
Pages (from-to)7592-7604
Number of pages13
JournalMolecular and Cellular Biology
Volume25
Issue number17
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

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Adipogenesis
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinase Kinases
90-kDa Ribosomal Protein S6 Kinases
Phosphotransferases
Ribosomal Protein S6 Kinases
PPAR gamma
Mitogen-Activated Protein Kinases
KSR-1 protein kinase
Cell Differentiation
Phosphorylation
Cell Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Kortum, R. L., Costanzo, D. L., Haferbier, J., Schreiner, S. J., Razidlo, G., Wu, M. H., ... Lewis, R. E. (2005). The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates adipogenesis. Molecular and Cellular Biology, 25(17), 7592-7604. https://doi.org/10.1128/MCB.25.17.7592-7604.2005

The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates adipogenesis. / Kortum, Robert L.; Costanzo, Diane L.; Haferbier, Jamie; Schreiner, Steven J.; Razidlo, Gina; Wu, Ming Hoi; Volle, Deanna J.; Mori, Toshiyuki; Sakaue, Hiroshi; Chaika, Nina V.; Chaika, Oleg V.; Lewis, Robert E.

In: Molecular and Cellular Biology, Vol. 25, No. 17, 01.09.2005, p. 7592-7604.

Research output: Contribution to journalArticle

Kortum, RL, Costanzo, DL, Haferbier, J, Schreiner, SJ, Razidlo, G, Wu, MH, Volle, DJ, Mori, T, Sakaue, H, Chaika, NV, Chaika, OV & Lewis, RE 2005, 'The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates adipogenesis', Molecular and Cellular Biology, vol. 25, no. 17, pp. 7592-7604. https://doi.org/10.1128/MCB.25.17.7592-7604.2005
Kortum, Robert L. ; Costanzo, Diane L. ; Haferbier, Jamie ; Schreiner, Steven J. ; Razidlo, Gina ; Wu, Ming Hoi ; Volle, Deanna J. ; Mori, Toshiyuki ; Sakaue, Hiroshi ; Chaika, Nina V. ; Chaika, Oleg V. ; Lewis, Robert E. / The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates adipogenesis. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 17. pp. 7592-7604.
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