Unit 1- Signal Transduction

Question 1

What are the 3 main amplification systems?

Answer 1

• allosteric enzyme regulation
• inter conversion cycle
• enzyme cascade

Question 2

What acceptors does PKA phosphorylate (ie activate)?

Answer 2

• enzymes
• structural proteins (troponin, myosin light chain kinase)
• ion channels (IP3 sensitive Ca channel)
• transcription factors (CRE, CREB)

Question 3

What are the groups of types of receptors in signal transduction?

Answer 3

• mem. bound R
• cytosilic R
• Nuclear R

Question 4

What are the targets of Ca2+ activated acceptors?

Answer 4

• directly activated by Ca2+ (tissue transglutaminase, PKC, phospholipase A2, calpain, DNases)
• Ca sensing regulatory subunits (calmodilin regulated proteins)

Question 5

What are the targets of Protein Kinase C (PKC) activated acceptors?

Answer 5

• cell surface receptors (EGF, CD3, insulin)
• enzymes (raf1, kinase, GAP-p21ras)
• ion channels (Na+/H+ exchange)
• proteins in cell cycle control (DNA topoisomerase)
• nuclear factors (NFKB)
• proteins in cytoskeleton (MARCKS)

Question 6

What is an eg. of 1 hydrophobic domain receptor with enzyme activity?

Answer 6

Receptor Tyrosine Kinase (RTK) -> insulin receptor

Question 7

What 3 main signal transduction pathways start with RTK?

Answer 7

• Ras (cell proliferation)
• PLC (cell proliferation + differentiation)
• PI3K (cell survival + metabolism)

Question 8

What does the Ras pathway result in?

Answer 8

• activate MAPK amplification cascade
• activate enzymes (eg. Raf)
• drives cell division, motility and survival

Question 9

How is Ras implicated in cancer?

Answer 9

Freq. mutated oncogenes = gain of fnx. Affects GTP binding = prolonged Ras activation

Question 10

How can Ras be inhibited?

Answer 10

• by itself

- faster by + GAP

Question 11

What is the insulin signaling mediator (ie recognize PIP3) of PI3K?

Answer 11

Akt (PKB)

Question 12

What are Akt/PKB’s Acceptor proteins?

Answer 12

mTOR (activate = cell growth + metabolism)

Bad, Bim, FoxO (inhibit as poor-apoptotic)

GLUT4 (activate = increase glucose uptake)

GSK3 (inhibit = cell cycle progression)

Question 13

What does Akt do I’m cancer?

Answer 13

Amplified activity

Question 14

Where is Nitric Oxide synthesized?

Answer 14

• endothelial cells
• neuronal cells
• macrophages

Question 15

What controls the synthesis of NOS.

Answer 15

Hormones, cytokines, bacterial endotoxins via

• reg. Intracellular Ca2+ levels (eNOS & nNOS)
• reg. Synthesis of NOS on gene level (iNOS)

Question 16

What are the effects of NO signaling (via increase cGMP)?

Answer 16

Increase vasodilation

Decrease BP

Decrease platelet aggregation

Question 17

What happens to Class I Nuclear Receptors when hormones bind to it?

Answer 17

Dissociation of heat shock proteins (HSP)

Dimerisation

Translocation -> nucleus

Question 18

What happens to Class I Nuclear R. In the nucleus?

Answer 18

+ specific sequence of DNA -hormone response element (HRE)

Recruitment of additional proteins (incl. RNA polymerase) to NR/DNA complex to transcribe DNA -> mRNA = bio response

Question 19

What is an eg. of a Class I Nuclear R.?

Answer 19

Steroid receptor family

Question 20

What is the fnx. of steroid R family?

Answer 20

Mediates changes in gene transcription

• slow onset
• long duration

Question 21

What is special about Class II Nuclear R.?

Answer 21

Retained in nucleus even when no ligand bound

Question 22

What does ligand binding to Class II Nuclear R. Result in?

Answer 22

Dissociation of corepressor protein

Recruitment of coactivator protein

Recruitment of additional proteins (incl. RNA polymerase) to NR/DNA complex to transcribe DNA -> mRNA = bio response

Question 23

What are some eg. of Class II Nuclear R.?

Answer 23

Retinoic acid R

Retinoid X R

Vit D R (VDR)

Thyroid hormone R

Peroxisome proliferator activated R (PPAR)