Transcript TGFb –Superfamily Proteins

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 CoSmads 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