TY - JOUR
T1 - Rac is activated by tumor necrosis factor α and is involved in activation of Erk
AU - Nosaka, Yurika
AU - Arai, Ayako
AU - Kanda, Eiichiro
AU - Akasaki, Takashi
AU - Sumimoto, Hideki
AU - Miyasaka, Nobuyuki
AU - Miura, Osamu
N1 - Funding Information:
We are grateful to Drs. Yoshimi Takai and Michael Karin for the generous gifts of experimental materials. This work was supported in part by grants from the Ministry of Education, Science, and Culture of Japan, and from the Ichiro Kanehara Foundation.
PY - 2001
Y1 - 2001
N2 - Tumor necrosis factor α (TNFα) activates various signal transduction pathways including those involving phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinases (Erk), c-Jun N-terminal protein kinases (JNK), and p38 kinases. Using the Rac binding domain of PAK (PAK-RBD) as an activation-specific probe, here we demonstrate that TNFα very rapidly and transiently activates the Rho family GTPase Rac in L929 cells. The PI3K inhibitor LY294002 significantly inhibited TNFα activation of Rac as well as Erk and abolished that of the PI3K target Akt, without showing any inhibitory effects on JNK and p38 activation. Furthermore, TNFα activation of Erk was abolished by a dominant negative Rac mutant, Rac17N, or by an activated Rac mutant, Rac12V. These findings suggest that Rac is activated by a mechanism that is at least partly dependent on PI3K in TNFα stimulated cells and plays a critical role in activation of the Erk signaling pathway.
AB - Tumor necrosis factor α (TNFα) activates various signal transduction pathways including those involving phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinases (Erk), c-Jun N-terminal protein kinases (JNK), and p38 kinases. Using the Rac binding domain of PAK (PAK-RBD) as an activation-specific probe, here we demonstrate that TNFα very rapidly and transiently activates the Rho family GTPase Rac in L929 cells. The PI3K inhibitor LY294002 significantly inhibited TNFα activation of Rac as well as Erk and abolished that of the PI3K target Akt, without showing any inhibitory effects on JNK and p38 activation. Furthermore, TNFα activation of Erk was abolished by a dominant negative Rac mutant, Rac17N, or by an activated Rac mutant, Rac12V. These findings suggest that Rac is activated by a mechanism that is at least partly dependent on PI3K in TNFα stimulated cells and plays a critical role in activation of the Erk signaling pathway.
KW - Akt
KW - Extracellular signal-regulated kinases
KW - Phosphatidylinositol 3-kinase
KW - Rac
KW - Tumor necrosis factor α
KW - c-Jun N-terminal protein kinases
KW - p38
UR - https://www.scopus.com/pages/publications/0034804474
UR - https://www.scopus.com/pages/publications/0034804474#tab=citedBy
U2 - 10.1006/bbrc.2001.5222
DO - 10.1006/bbrc.2001.5222
M3 - Article
C2 - 11453646
AN - SCOPUS:0034804474
SN - 0006-291X
VL - 285
SP - 675
EP - 679
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -