TGFb –Superfamily Proteins Erica DeGeus

TGFb (Transforming Growth Factor b)

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

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

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

Ribbon Diagram of mature TGFb dimer Figure 23-2

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

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

The End