TY - JOUR
T1 - The MAPK scaffold kinase suppressor of Ras is involved in ERK activation by stress and proinflammatory cytokines and induction of arthritis
AU - Fuselo, Angela M.
AU - Mandik-Nayak, Laura
AU - Shih, Fei
AU - Lewis, Robert E.
AU - Allen, Paul M.
AU - Shaw, Andrey S.
PY - 2006/11/1
Y1 - 2006/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33750322263&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.177.9.6152
DO - 10.4049/jimmunol.177.9.6152
M3 - Article
C2 - 17056543
AN - SCOPUS:33750322263
VL - 177
SP - 6152
EP - 6158
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -