TGFB Signalling Pathways

Question 1

What is TGFB?

Answer 1

Transforming growth factor beta 1: Is a prototype of a family of signalling molecules that includes important cellular transformations or differentiations.

Question 2

How are TGFB discovered?

Answer 2

Studies of development.

Question 3

What do TGFB affect?

Answer 3

Cell proliferation, differentiation and migration.

Question 4

What happens if the TGFB has a mutation?

Answer 4

They will have strong, specific effects on embryonic development.

Question 5

What was TGFB first classified as? What is it classified as now?

Answer 5

An oncogene.

A tumor suppressor.

Question 6

Oncogenes vs tumor suppressor?

Answer 6

Oncogenes: Cause cancer if they are permanently turned on.

Tumor Suppressor: Cause cancer if they are permanently turned off.

Question 7

What are the three families of the TGFB?

Answer 7

1. TGFB Family
2. Activin Family
3. Bone morphogenic protein

Question 8

What does the TGFB family do?

Answer 8

Inhibit cell growth/division, induce formation of extracellular matrix.

Question 9

What does the activin family do?

Answer 9

Early embryonic development.

Question 10

What does activin itself stimulate? Inhibin?

Answer 10

Stimulate pituitary to release FSH, a key step in ovulation.

Inhibin prevents FSH release.

Question 11

What does bone morphogenic protein (BMP)?

Answer 11

Involved in many developmental processes.

Question 12

What are TGFB family ligands typically?

Answer 12

Dimers.

Question 13

What are the TGFB dimers usually made of and how are they held together?

Answer 13

They are dimers made of identical subunits, held together by three disulfide bonds.

Question 14

What are the three disulfide bonds of the TGFB dimers made of?

Answer 14

Three cysteine residues called the cystine knot.

Question 15

What are inhibit and some of the BMPs classified as?

Answer 15

Heterodimeric (two different polypeptides).

Question 16

What are the two receptors of the TGFB family ligands?

Answer 16

They are also dimers, and type I and type II.

Question 17

What makes each type I and type II receptor?

Answer 17

Each as an extracellular domain, a single transmembrane domain, and a cytoplasmic domain.

Question 18

What do these receptors resemble?

Answer 18

Growth factor receptors.

Question 19

What are the two key differences between growth factor receptor and TGFB receptors?

Answer 19

1. Productive ligand binding requires both a Type I and a Type II dimer to come together. A assembled receptor is a tetramer.
2. The cytoplasmic domains of the receptors contain a Ser/Thr-specific rather than Try-specific protein kinase.

Question 20

What is the difference between the amino acid sequences of type I and type II receptors?

Answer 20

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.

Question 21

What are the three ways of ligand binding?

Answer 21

1. Ligand binds to type I dimer then dimerization of type II.
2. Ligand binds to type II dimer the dimerization of type I.
3. Type-I, Type II receptor complex forms first and then the ligand binds.

Question 22

Which type of receptors use which ligand binding methods?

Answer 22

1. TGFB
2. BMP
3. TGFB