NF-kB signaling pathway

[Dr.serotonin]

any one who has a good grasp of this pathway plz explain this to me or give a link of it. i cant find a good source to study it. thnx

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[MudPhud20XX]

yeah this is one of the tricky cocepts out there that no one really explains it well. As far as step 1 is concerned, just know that NF-KB is a response element (binding site) for NFKB (nuclear factor Kappa-B), which is a transcription factor that turns on a lot things needed for acute inflammation such as IL-2, BCL (for apoptosis), and light chain immunoglobin which will stimulate NK cells, CD4 helper cells, CD8 cytotoxic T cells

Also know that corticosteroids directly block NF-KB.

In endocrinology, know that RANK-L stands for receptor activator of NF-KB ligand this is from FA.

So inc PTH stimulates macrophages CSF and RANK-L secreted by osteoblast. RANK-L binds to RANK on osteoblast and this interaction stiumates the osteoclast. RANK is a receptor that belongs to TNF receptor family, so they are all involved in the inflammatory process in our body.

hope this helps.

 

[Dr.serotonin]

thanks a lot . actually I came across a Question regarding NF-kB in nbme 15 and unfortunately they were asking about IkB which is inhibitor of NF-KB; they were asking it's role in the formation of IL-6.

 

[dirty630]

thanks a lot . actually I came across a Question regarding NF-kB in nbme 15 and unfortunately they were asking about IkB which is inhibitor of NF-KB; they were asking it's role in the formation of IL-6.

When something like TNF-a or RANKL bind a cell, they activate a kinase cascade. Part of that cascade is Ik-K, (inhibitor of kB kinase), which phosphorylates IkB (inhibitor of kB). Ik-K's job is to keep NF-kB in the cytosol away from DNA so it can't act as a transcription factor. When Ik-K phosphorylates Ik-B, Ik-B gets ubiquitinated and degraded, and NF-kB is then free to go into the nucleus and help start transcription of proinflammatory cytokines.

 

[Dr.serotonin]

thanks a lot. this really helps

 

[rebel87]

When something like TNF-a or RANKL bind a cell, they activate a kinase cascade. Part of that cascade is Ik-K, (inhibitor of kB kinase), which phosphorylates IkB (inhibitor of kB). Ik-K's job is to keep NF-kB in the cytosol away from DNA so it can't act as a transcription factor. When Ik-K phosphorylates Ik-B, Ik-B gets ubiquitinated and degraded, and NF-kB is then free to go into the nucleus and help start transcription of proinflammatory cytokines.

Useful explanation. There is a error in typing: Ik-K's job is to keep NF-kB in the cytosol away from DNA so it can't act as a transcription factor.
This must be: IkB instead of IkK.

 

[Mr.Scalpel]

Necro'ing:

 

[WeedForLunch]

Google it and memorize it.. It's in more than 1 place...not just NBME 15

NF-KB is made up of a heterodimer : RelA and p50..
NF-KB resides in the cytoplasm as a heterodimer made out of these 2 components.
Normally, NF-KB heterodimer is inactive.. It is present in the inactive state because of binding of NF-KB with IKB ∝(Inhibitor of Kappa Beta)

Now when signal is transferred from the extracellular environment into the cell using : TLR (Toll Like Receptor) binding to PAMP/DAMP then it stimulates the activation of IKK (Inhibitor of Kappa Kinase)
Inhibitor of Kappa Kinase(IKK) will phosphorylate IKB∝ which is the protein that normally is attached to and inhibits NF-KB..
Because of phosphorylation of IKB∝ by IKK.. it detaches from NF-KB and NF-KB becomes activated.. After phosphorylation IKK is poly-ubiquinated and subsequently broken down by proteasome..
Activated NF-KB moves from Cytoplasm to Nucleus and attaches to RE (Response Elements) on the DNA..

This attachment leads to transcription and translation of CAM (Cell Adhesion molecules), ILs, Cytokines, APR, etc other inflammatory mediator output.
It also stimulates synthesis of IKB∝ ... which means that as a part of NF-KB activity there is self-regulation which will inhibit activity of NF-KB itself.