TGF b –Superfamily Proteins

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 50-375 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 110-140 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