TGFB Signalling Pathways Flashcards
What is TGFB?
Transforming growth factor beta 1: Is a prototype of a family of signalling molecules that includes important cellular transformations or differentiations.
How are TGFB discovered?
Studies of development.
What do TGFB affect?
Cell proliferation, differentiation and migration.
What happens if the TGFB has a mutation?
They will have strong, specific effects on embryonic development.
What was TGFB first classified as? What is it classified as now?
An oncogene.
A tumor suppressor.
Oncogenes vs tumor suppressor?
Oncogenes: Cause cancer if they are permanently turned on.
Tumor Suppressor: Cause cancer if they are permanently turned off.
What are the three families of the TGFB?
- TGFB Family
- Activin Family
- Bone morphogenic protein
What does the TGFB family do?
Inhibit cell growth/division, induce formation of extracellular matrix.
What does the activin family do?
Early embryonic development.
What does activin itself stimulate? Inhibin?
Stimulate pituitary to release FSH, a key step in ovulation.
Inhibin prevents FSH release.
What does bone morphogenic protein (BMP)?
Involved in many developmental processes.
What are TGFB family ligands typically?
Dimers.
What are the TGFB dimers usually made of and how are they held together?
They are dimers made of identical subunits, held together by three disulfide bonds.
What are the three disulfide bonds of the TGFB dimers made of?
Three cysteine residues called the cystine knot.
What are inhibit and some of the BMPs classified as?
Heterodimeric (two different polypeptides).
What are the two receptors of the TGFB family ligands?
They are also dimers, and type I and type II.
What makes each type I and type II receptor?
Each as an extracellular domain, a single transmembrane domain, and a cytoplasmic domain.
What do these receptors resemble?
Growth factor receptors.
What are the two key differences between growth factor receptor and TGFB receptors?
- Productive ligand binding requires both a Type I and a Type II dimer to come together. A assembled receptor is a tetramer.
- The cytoplasmic domains of the receptors contain a Ser/Thr-specific rather than Try-specific protein kinase.
What is the difference between the amino acid sequences of type I and type II receptors?
The type I receptors have an extra Gly-Ser rich region (the GS domain) just inside the membrane.
The type II receptors are a little longer overall.
What are the three ways of ligand binding?
- Ligand binds to type I dimer then dimerization of type II.
- Ligand binds to type II dimer the dimerization of type I.
- Type-I, Type II receptor complex forms first and then the ligand binds.
Which type of receptors use which ligand binding methods?
- TGFB
- BMP
- TGFB