1. Chapter 14: Signaling Pathways That Control Gene Activity
By: Nick Chubb

2. TGFb= Transforming Growth Factor b
TGFb Is Often Refered to as Super-Family Proteins These molecules play an important role in extracellular signaling for the development of eukaryotes These molecules result from inactive precursor proteins though proteolythic processing These inactive precursor proteins contain an N- terminus peptide (leading group), a pro-domain containing anywhere from 50 to 375 amino acids, and an C-terminus for the tail. (mature domain) The C-terminus forms the active growth factor.

3. This shows the formation of TGFb Growth Factors

4. TGFb Growth Factors
1. Promote molecules for Cell Adhesion Promote production of Molecules in the Extracellular Matrix Respondsible for Production of Various Other Growth Factors

5. 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.

6. This is a representaion of the signal pathway by ligand reception

7. This shows the ribbon diagram of the mature TGFb Molecule

8. 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.

9. 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.

10. QUESTIONS?????
Thank You…..