Pathway maps

IL-1 beta-dependent CFTR expression
IL-1 beta-dependent CFTR expression

Object List (links open in MetaCore):

TAK1(MAP3K7), IL-1RI, TRAF6, TAB1, CFTR, NF-kB p50/p65, TAB2, IL-1 beta, IRAK1/2, TOLLIP, MyD88, IL1RAP, IKK, IRAK4, NIK(MAP3K14), I-kB

Description

IL-1 beta-dependent CFTR expression

Interleukin 1 ( IL-1 beta ) stimulates expression of the Cystic fibrosis transmembrane conductance regulator ( CFTR ) via Nuclear factors of kappa light polypeptide in B-cells ( NF-kB ). The exact signaling leading to CFTR expression is unknown. The basic pathway of NF-kB activation by IL-1 beta is mediated by TNF receptor-associated factor 6 ( TRAF6 ). IL-1 binds to Interleukin 1 receptor type I ( IL-1RI ) and activates transcription factors via cytoplasmic mediators such as myeloid differentiation primary response gene ( MyD88 ), IL-1 receptor-associated kinase ( IRAK ) and TRAF6 [1], [2]. These intracellular processes result in recruitment and activation of I kappa B kinases complex ( IKK ). IKK phosphorylates NF-KB inhibitor ( I-KB ) and thereby marks it for degradation, consequently leading to increase in DNA-binding activity of the NF-kB [3] that directly activates transcription of CFTR [4], [5].

References:

  1. Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K
    The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 1999 Mar 18;398(6724):252-6
  2. Akira S
    Toll-like receptor signaling. The Journal of biological chemistry 2003 Oct 3;278(40):38105-8
  3. Yamamoto Y, Gaynor RB
    IkappaB kinases: key regulators of the NF-kappaB pathway. Trends in biochemical sciences 2004 Feb;29(2):72-9
  4. Brouillard F, Bouthier M, Leclerc T, Clement A, Baudouin-Legros M, Edelman A
    NF-kappa B mediates up-regulation of CFTR gene expression in Calu-3 cells by interleukin-1beta. The Journal of biological chemistry 2001 Mar 23;276(12):9486-91
  5. Cafferata EG, Guerrico AM, Pivetta OH, Santa-Coloma TA
    NF-kappaB activation is involved in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) by interleukin-1beta. The Journal of biological chemistry 2001 May 4;276(18):15441-4