Second Messengers and Intracellular Signal Transduction Pathways Flashcards
How is the presence of a ligand sensed by a cell
When a receptor is bound it activates a pathway
How is information transmitted further into the cell from the receptor
Through a signal transduction pathway:
conformational changes
protein-protein interactions
generation of second messengers
post-translational modifications
What do G-protein conformational changes activate
Heterotrimeric G-protein subunits activate
Which G-protein subunit dissociates when bound by GTP
Alpha
What causes the alpha subunit to return to the receptor
GTP hydrolysis to GDP
What type of receptor dimerizes when bound by a receptor
Enzyme-coupled
What phosphorylates CDKs
CDK activating kinases (CAKs)
What happens to CDKs when phosphorylated
A conformational change allows full activation of the CDK allowing a closer fit with cyclin
Which kinase has inhibiting phosphorylation that stops CDKs
Wee-1
What is a signal cascade
Each event directly leads to the activation of the next downstream event. Linear/hierarchal
Protein kinase A is complex of what
regulatory proteins and catalytic subunits
What activates PKA
cAMP binding to R subunits
What does PKA regulate and what does each target cause
Ca2+ handling proteins - muscle contraction/ relaxation
Metabolic enzymes - release of glucose
transcription factors - transcription (CREB)
What activates CREB and where does CREB bind
PKA
CREB regulatory elements in target genes
What does the phosphorylation of CREB allow
Binding of CREB binding protein (CBP) which can then promote transcription
How does IP3 enter the cell and where does it bind
Passive diffusion
smooth ER Ca2+ channel receptors
What happens when IP3 binds its intracellular target
activation of calcium-regulated signalling proteins including membrane calcium channels
h=greater increase of Ca2+ levels
Explain the MAPK pathway
GTP-bound Ras binds MAP kinase kinase kinase (Raf)
Which phosphorylates MAP kinase kinase (MEK)
Which phosphorylates MAP kinases (Erk1 and Erk2)
Activated MAPKs enter the nucleus and activate transcription factors
How are signalling cascades organised in 3D space
scaffolding proteins enhance specificity and proximity of proteins
Why do signals need to be amplified
random fluctuations (noise) are filtered out
minimise cell function occurring by chance
How do you amplify or limit the activity of a signalling pathway
changing ligand concentration
changing receptor concentration
using signal amplification eg enzyme cascades
Explain a positive feedback loop
when a molecule has a stimulating effect on a molecule upstream of it
Explain a negative feedback loop
when a molecule has an inhibitory effect on a molecule upstream of it
