Transcript Chapter 14: Signaling Pathways That Control Gene Activity

Chapter 14: Signaling
Pathways That Control
Gene Activity
By: Nick Chubb
TGFb= Transforming
Growth Factor b
TGFb Is Often Refered to as Super-Family Proteins
1.These molecules play an important role in
extracellular signaling for the development of
eukaryotes.
2.These molecules result from inactive precursor
proteins though proteolythic processing.
3.These inactive precursor proteins contain an Nterminus peptide (leading group), a pro-domain
containing anywhere from 50 to 375 amino acids,
and an C-terminus for the tail. (mature domain)
4.The C-terminus forms the active growth factor.
This shows the formation of TGFb Growth Factors
TGFb Growth Factors
1. Promote molecules for Cell Adhesion
2. Promote production of Molecules in the
Extracellular Matrix
3. Respondsible for Production of Various
Other Growth Factors
Formation and Structure
of TGFb Superfamily of
Signaling molecules
The TGFb precursors are cleaved soon after being
secreted. The pro-domain and mature domain are
stored in the extracellular matrix in a complex that
also contains latent TGFb-binding protein (LTBP).
The mature domain contains six conserved cystein
residues, which form three intrachain disulfide
bonds and also a single disulfide bond connecting
two monomers. Following proteolysis or a
conformational change in LTBP, the active homo- or
heterodimeric protein is released.
This is a representaion of the signal pathway by ligand reception
This shows the ribbon diagram of
the mature TGFb Molecule
TGFb Signaling Pathway
Stimulation by TGFb leads to activation of the intrinsic
serine/threonine kinase activity in the cytosolic domain of the type I
(RI) receptor, which then leads to phosphorylation of an R-Smad,
exposing a nuclear-localization signal.
After Phosphorylated R-Smad binds a co-Smad, the resulting
complex translocates into the nucleus, where it interacts with various
transcription factors to induce expression of targeted genes.
Oncoproteins (Ski and SnoN) and (Smad7) act as negative regulators
of TGFb signaling.
TGFb signaling generally inhibits cell proliferation. Loss of various
components of the signaling pathway contributes to abnormal cell
proliferation and malignancy.
SUMMARY!!!
Binding of TGFb to its receptors can elicit a
variety of responses in different cell types.
For example: TGFb induces plasminogen
activator inhibitor in epithelial cells and
specific immunoglobulins in B cells.
In both cell Types, Smad3 is activated.
These are just a few of the many signal
pathways that are influenced by TGFb.
QUESTIONS?????
Thank You…..