1. TGFb –Superfamily Proteins
Erica DeGeus

2. TGFb (Transforming Growth Factor b)

3. What makes up the TGFb –Super Family Proteins?
A number of related extracellular signaling molecules that play widespread roles in regulating development in both invertebrates and vertebrates
These are derived from inactive precursor proteins through proteolytic processing
The precursors contain an N-terminal signal peptide, a central pro-domain containing amino acids, and a C-terminal mature domain
The C-terminal mature domain forms the active growth factor

5. These growth factors also promote the production of:
Cell-adhesion molecules
Other growth factors
Extracellular matrix molecules

6. The monomeric form of these growth factors contains amino acids and has a compact structure with four antiparallel b strands and three intramolecular disulfide linkages forming a structure called a cystine knot
The cystine knot is resistant to denaturation which may be particularily well suited for extracellular molecules

7. Ribbon Diagram of mature TGFb dimer
Figure 23-2

8. TGFb– Signaling Pathway
The ligand binds to type I and type II receptors (which are serine/threonine kinases) and induces formation of multimeric receptors
Type II receptors phosphorylate type I receptors in the juxtamembrane region
Activated type I receptors specifically phosphorylate receptor-regulated Smads (R-Smads), which then dimerize with Co-Smads in the cytosal

9. The R-Smad/Co-Smad complex translocates to the nucleus where it binds to regulatory sequences in combination with specific transcription factors, leading to transcription of specific target genes

11. The End