Biomedical Engineering Reference
In-Depth Information
TFs
transcription factors
TNF-α
tumor necrosis factor α
VACM-1
vascular adhesion molecule 1
VLA-4
very late activation antigen 4
Vps34
vacuolar protein-sorting defective 34
Key Facts about the PI3K/Akt-NF-
k
B Signaling Pathways
1. h e PI3K/Akt-NF-κB signaling pathways are ubiquitously expressed,
including inl ammatory cells and vascular endothelium.
2. Cytokines, chemokines, and inl ammatory agents activate PI3Ks, which
generate PIP2 and PIP3 in the plasma membrane of target cells.
3. PIP2 and PIP3 bind to the pleckstrin homology (PH) domain of Akt and
cause Akt activation.
4. Akt directly phosphorylates IKKα and the latter results in the
phosphorylation and degradation of IκB in the NF-κB signaling pathway.
5. NF-κB is freed and translocated into the nucleus of the cell with increased
NF-κB binding activity to the promoters of the adhesion molecule genes,
such as VCAM-1, E-selectins, and integrins.
6. Together with other transcription factors, there is an upregulation of
adhesion molecules, which will facilitate the interaction between the
inl ammatory cells and endothelial cells.
7. h e enhanced adhesion molecule gene expression in these cells together
with other chemoattractants produced by the local cells or tissues will
facilitate the extravasation of the leukocyte into the inl ammation foci.
8. Manipulation of PI3K and NF-κB activity in the cells with chemical agents
or dominant negative proteins may regulate adhesion molecule gene
expression and modulate the inl ammatory process.
Definition of Terms
Heterodimer:
A protein complex consisting of dif erent units.
Homodimer:
A protein complex formed by two identical units.
Inl ammatory proteins:
Cytokines, chemokins, adhesion molecules and other proteins that
play critical roles in inl ammatory response.
Leukocyte extravasation:
Process by which leukocytes emigrate from the circulation into
the inl ammatory foci and tissues.
Signaling transduction pathways:
Networks consisting of a series of dif erent components
in a certain order to transmit and execute a specii c cell signal for its specii ed function
or activities.
