Chapter 21

Signal Transduction Questions

1. Receptors which lead to the inhibition of adenylate cyclase must first activate

  1. protein kinase C
  2. protein kinase A
  3. heterotrimeric G proteins
  4. small G proteins
  5. phospholipase C

2. Water insoluble steroid hormones primarily exert their effect by:

  1. Activating a Ras dependent pathway
  2. Binding to cell surface receptors
  3. Migrating to the nucleus where it can bind to transcription factors and activating them
  4. By inhibiting guanylate cylclase

3. Receptor tyrosine kinases

  1. Are seven transmembrane receptors
  2. Activate there targets via the G protein cascade
  3. Are called so due to an unusually high content of tyrosine residues
  4. Interact with their targets via SH2/SH3 domains

4. The guanylyl cyclase (cGMP) system is unique form the adenylate cyclase system in that

  1. The first messenger is not a peptide hormone
  2. The first messenger is a short lived molecule
  3. The receptor has integral enzymatic activity producing cGMP
  4. The first messenger is nitric oxide (NO)
  5. All of the above

None of the above

5. Peptide growth factors

  1. Usually function through the binding intracellular protein kinases and activating them
  2. Do not require second messenger systems
  3. Are usually involved with receptors which contain tyrosine kinase activity
  4. None of the above

6. Which of the following statements about ras is true:

  1. ras has seven transmembrane domains
  2. ras is a protein kinase
  3. ras is direct activator of jun kinase (JNK)
  4. ras contains SH2 and SH3 domains
  5. ras is activated by the exchange factor SOS

7. T/F seven pass receptors often contain an integral tyrosine kinase activity

8. Which of the following statements about inositol 1,4,5 trisphosphate (IP3) are correct?

  1. IP3 leads to the uptake of calcium by the mitochondria
  2. IP3 concentration may be decreased by lithium
  3. IP3 reacts directly and activates protein kinase C (PKC)
  4. IP3 opens calcium channels in the perinuclear regions of the endoplasmic reticulum

9. Receptor tyrosine kinases:

  1. contain a seven transmembrane domain:
  2. dimerize and autophosphorylate upon ligand binding
  3. are similar in structure and function to G-protein linked receptors
  4. are not found associated with certain types of cancer

10. The activation of the a subunit of a heterotimeric G-protein results in:

  1. a tighter binding between the a , ß and g subunits
  2. an increase in only PLCg
  3. the separation of the a and ß g subunits to interact with their effector proteins
  4. a loss in farnesyl of the ß subunit

11. Which of the following statements about ras is true:

  1. ras has seven transmembrane domains
  2. ras is a protein kinase
  3. ras is direct activator of jun kinase (JNK)
  4. ras contains SH2 and SH3 domains
  5. ras is activated by the exchange factor SOS

12. The following statements about G-coupled protein signal transduction are true except:

  1. all heterotrimeric G-proteins have an a , ß and a g subunit
  2. Heterotrimeric G-proteins are coupled to receptors with seven transmembrane spanning domains
  3. The ß and g subunits can be responsible for activation of certain effector activties
  4. The ß -subunit binds and hydrolyzes GTP

13. a adrenergic receptors are usually linked to which specific G protein?

a) GaI c) Gas

c) Gaq d) Ga12

e)Golf

14. G proteins of the Gi family are involved in what signaling pathway _____________________

 

15. An example of a class 2 tyrosine kinase receptor is

  1. The insulin receptor
  2. The epidermal growth factor (EGF) receptor
  3. The platelet derived growth factor (PDGF) receptor
  4. The fibroblast growth factor (FGF) receptor

 

16. How is the regulation of the enzymatic activity of both protein kinase C (PKC) and protein kinase A (PKA) similar?

 

 

17. GTPg S is often used to determine the role of G proteins in signaling. Why is this an effective tool?

 

18. What would be the effect of a mutation in the gene for a beta subunit of G proteins that leads to a decreased interaction with the g subunit?

 

19. What structural alterations are involved when the alpha subunit of a G protein interacts with the beta and gamma subunits.

20. Explain the mechanism and result of cholera toxin.

21. Which phospholipase C isozyme would you most expect to be involved with a viral Src infected cell?

 

22. You have purified and cloned a membrane protein and believe it to be a hormone receptor you call the dragon receptor. You have tested the effects of the dragon receptor on a variety of cells and found that it increases the DNA activity (transcription of various genes) of these cells. You have also seen an increase in intracellular calcium after activating the dragon receptor with the appropriate hormone. Treatment with both pertusis toxin and protein kinase C dramatically inhibit the dragon receptor actions on DNA transcription. What intracellular signaling pathway would you hypothesize is employed by the dragon receptor? Are any of these proteins potential oncogenes?

 

  1. What exactly is signal transduction and how do the terms cascade and amplification apply to this field?

 

24. To earn your Nobel prize you have been working on signal transduction in a cell line found only in Dragons. When you add lysophosphatidic acid (LPA, a G12 receptor linked activator) to cultured dragon cells, you observe an increase in cell growth, an increase in GTP binding to ras and the activation of genes typically under the control of the transcription factors Jun and Fos. You have clones for the a subunit and the bg subunits. When you transfect and express these clones in the cells, the a subunit has little effect yet the bg subunits lead to a considerable activation on cell growth, ras and the Jun Fos activated genes. Addition of genistein a very potent tyrosine kinase inhibitor has no effect when you add LPA or the clones to the cells. In parallel studies infection of your cells with a viral oncogene also leads to the activation of cell growth, ras, Jun and Fos. However, addition of genistein in the infected cells does inhibit the activation of for each of the proteins and cell growth.

 

What pathway do you believe is being activated?

How are these cells different from the typical means of activation?

Explain the differences in the LPA and viral infection activation of this pathway.

Propose the pathway for this pathway.

Design additional experiments to determine additional members of the signaling pathway. At your disposal are inhibitors for each and every kind of protein we have studied so far.