Developmental Signals - TGF-beta

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Introduction

Transforming Growth Factor-beta (TGF-β)

TGF-beta signaling pathway[1]
Factor Links: AMH | hCG | BMP | sonic hedgehog | bHLH | HOX | FGF | FOX | Hippo | LIM | Nanog | NGF | Nodal | Notch | PAX | retinoic acid | SIX | Slit2/Robo1 | SOX | TBX | TGF-beta | VEGF | WNT | Category:Molecular

Some Recent Findings

Structure

The TGF precursor protein has three distinct regions:

  1. signal peptide - targets it to the endoplasmic reticulum and secretion
  2. propeptide - or the latency associated peptide
  3. mature peptide - cleaved from the precursor protein and is actively involved in signalling
  • cleaved by Furin - a convertase
  • cleaved at a dibasic arginine-X-X-arginine (RXXR) site

Function

Signaling Pathway

TGF-beta signaling pathway[1]

Receptor

  1. active peptide forms a hetero- or homodimer
  2. binds to a specific TGF-β Type II receptor
  3. Type II receptor then recruits a TGF-β Type I receptor
  4. phosphorylates it via its serine/threonine kinase domain
  5. phosphorylated Type I receptors then phosphorylate receptor-associated Smad proteins (R-Smads), including Smad1/5 and Smad2/3
  • Type II receptor - MlTgfRII
  • Type I receptors - MlTgfRIa, MlTgfRIb, and MlTgfRIc

Intracellular Signaling

  • R-Smad proteins are composed of two main functional domains
    • Mad-homology domains 1 and 2 (MH1 and MH2)
  • Smad1/5 - associated with BMP-like signalling.
  • Smad2/3 - associated with TGF-β-like signaling.

OMIM

About OMIM "Online Mendelian Inheritance in Man OMIM is a comprehensive, authoritative, and timely compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries contain copious links to other genetics resources." OMIM


References

  1. 1.0 1.1 Pang K, Ryan JF, Baxevanis AD, Martindale MQ (2011) Evolution of the TGF-β Signaling Pathway and Its Potential Role in the Ctenophore, Mnemiopsis leidyi. PLoS ONE 6(9): e24152 PLoS ONE
  2. <pubmed>20227380</pubmed>

Reviews

Articles

<pubmed>17077151</pubmed>

Online Textbooks

Search PubMed

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Cite this page: Hill, M.A. (2019, October 15) Embryology Developmental Signals - TGF-beta. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_TGF-beta

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G