Stimulation of NFκB activity by multiple signaling pathways requires PAK1

被引:157
作者
Frost, JA
Swantek, JL
Stippec, S
Yin, MJ
Gaynor, R
Cobb, MH
机构
[1] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA
[2] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA
关键词
D O I
10.1074/jbc.M909860199
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The p21-activated kinase (PAK1) is a serine-threonine protein kinase that is activated by binding to the Rho family small G proteins Rac and Cdc42hs. Both Rac and Cdc42hs have been shown to regulate the activity of the transcription factor NF kappa B. Here we show that expression of active Ras, Raf-1, or Rad in fibroblasts stimulates NF kappa B in a PAK1-dependent manner and that expression of active PAK1 can stimulate NF kappa B on its own. Similarly, in macrophages activation of NF kappa B as well as transcription from the tumor necrosis factor alpha promoter depends on PAK1. In these cells lipopolysaccharide is a potent activator of PAK1 kinase activity. We also demonstrate that expression of active PAK1 stimulates the nuclear translocation of the p65 subunit of NF kappa B but does not activate the inhibitor of kappa B kinases alpha or beta. These data demonstrate that PAK1 is a crucial signaling molecule involved in NF kappa B activation by multiple stimuli.
引用
收藏
页码:19693 / 19699
页数:7
相关论文
共 76 条
  • [1] PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia
    Abo, A
    Qu, J
    Cammarano, MS
    Dan, CT
    Fritsch, A
    Baud, V
    Belisle, B
    Minden, A
    [J]. EMBO JOURNAL, 1998, 17 (22) : 6527 - 6540
  • [2] ALKALAY I, 1995, MOL CELL BIOL, V15, P1294
  • [3] BAEUERLE PA, 1994, ANNU REV IMMUNOL, V12, P141, DOI 10.1146/annurev.immunol.12.1.141
  • [4] Apoptosis: Activate NF-kappa B or die?
    Baichwal, VR
    Baeuerle, PA
    [J]. CURRENT BIOLOGY, 1997, 7 (02) : R94 - R96
  • [5] The NF-kappa B and I kappa B proteins: New discoveries and insights
    Baldwin, AS
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 : 649 - 683
  • [6] Sequential DNA damage-independent and -dependent activation of NF-κB by UV
    Bender, K
    Göttlicher, M
    Whiteside, S
    Rahmsdorf, HJ
    Herrlich, P
    [J]. EMBO JOURNAL, 1998, 17 (17) : 5170 - 5181
  • [7] Activation of nuclear transcription factor NF-κB by interleukin-1 is accompanied by casein kinase II-mediated phosphorylation of the p65 subunit
    Bird, TA
    Schooley, K
    Dower, SK
    Hagen, H
    Virca, GD
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (51) : 32606 - 32612
  • [8] TARF6 is a signal transducer for interleukin-1
    Cao, ZD
    Xiong, J
    Takeuchi, M
    Kurama, T
    Goeddel, DV
    [J]. NATURE, 1996, 383 (6599) : 443 - 446
  • [9] IKAP is a scaffold protein of the IκB kinase complex
    Cohen, L
    Henzel, WJ
    Baeuerle, PA
    [J]. NATURE, 1998, 395 (6699) : 292 - 296
  • [10] A cytokine-responsive I kappa B kinase that activates the transcription factor NF-kappa B
    DiDonato, JA
    Hayakawa, M
    Rothwarf, DM
    Zandi, E
    Karin, M
    [J]. NATURE, 1997, 388 (6642) : 548 - 554