TGFb

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TGFb Superfamily Proteins

• Erica DeGeus

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• TGFb (Transforming Growth Factor b)

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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

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These growth factors also promote the production
of

• Cell-adhesion molecules
• Other growth factors
• Extracellular matrix molecules

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• 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

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Ribbon Diagram of mature TGFb dimer
Figure 23-2
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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

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• 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

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The End