week 2 - second messenger pathways

Question 1

are skin cells impermeable

Answer 1

yes

Question 2

what biological outputs can be generated by signal transduction pathways

Answer 2

1. conformational changes
2. changes in protein-protein interactions
3. generation of second messengers
4. post translational modifications

Question 3

what format do intracellular signalling pathways follow

Answer 3

a linear signalling cascade

• each event leads to the activation of the next downstream event
• leads to the activation of another event and so on

Question 4

what happens at each level of intracellular signalling pathways

Answer 4

mechanisms may be used to ‘switch on’/’switch off’ the signalling molecule that functions at that level

Question 5

describe the pathway

Answer 5

ligand -> receptor -> membrane associated effector -> second messenger -> first intracellular target

Question 6

what is protein kinase A

Answer 6

PKA is a major cellular target of cAMP

-PKA is a complex of regulatory (R) and catalytic (C) subunits
-this complex is activated by binding of cAMP molecules to the R subunits
-the catalytic subunits are released as catalytically active enzymes
-metabolism of cAMP by phosphodiesterase (PDEs) inactivates the pathway

Question 7

explain the major substrate of PKA

Answer 7

• CREB transcriptional regulatory proteins can directly bind to specific elements (CRE) in its target genes in a constitutive manner but unless its phosphorylated it is not transcriptively active

-phosphorylation of CREB allows it to bind to another transcriptional regulator known as CBP (CREB binding protein)

-phospho- CREB/CBP complexes can then promote transcription of their target genes