The MAPK scaffold kinase suppressor of Ras is involved in ERK activation by stress and proinflammatory cytokines and induction of arthritis

Angela M. Fuselo, Laura Mandik-Nayak, Fei Shih, Robert E Lewis, Paul M. Allen, Andrey S. Shaw

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The MAPK ERK is required for LPS-induced TNF production by macrophages. Although the scaffold kinase suppressor of Ras (KSR)1 is required for efficient Erk activation by mitogenic stimuli, the role of KSR1 in ERK activation by inflammatory and stress stimuli is unknown. In this study, we examined the effects of KSR deficiency on ERK activation by stress stimuli and show that ERK activation by TNF, IL-1, and sorbitol is attenuated in the absence of KSR1. To determine the significance of this defect in vivo, we tested KSR-deficient mice using a passive transfer model of arthritis. We found that the induction of arthritis is impaired in the absence of KSR. Thus, KSR plays a role in ERK activation during inflammatory and stress responses both in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)6152-6158
Number of pages7
JournalJournal of Immunology
Volume177
Issue number9
StatePublished - Nov 1 2006

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Mitogen-Activated Protein Kinase Kinases
Arthritis
Cytokines
Sorbitol
Interleukin-1
Macrophages
KSR-1 protein kinase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The MAPK scaffold kinase suppressor of Ras is involved in ERK activation by stress and proinflammatory cytokines and induction of arthritis. / Fuselo, Angela M.; Mandik-Nayak, Laura; Shih, Fei; Lewis, Robert E; Allen, Paul M.; Shaw, Andrey S.

In: Journal of Immunology, Vol. 177, No. 9, 01.11.2006, p. 6152-6158.

Research output: Contribution to journalArticle

Fuselo, Angela M. ; Mandik-Nayak, Laura ; Shih, Fei ; Lewis, Robert E ; Allen, Paul M. ; Shaw, Andrey S. / The MAPK scaffold kinase suppressor of Ras is involved in ERK activation by stress and proinflammatory cytokines and induction of arthritis. In: Journal of Immunology. 2006 ; Vol. 177, No. 9. pp. 6152-6158.
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