Signaling: Ser/Thr Protein Kinases Flashcards
What is the action of kinases?
add phosphate (phosphorylate) to proteins to regulate their activity
What opposes the action of kinases?
phosphatase -> dephosphorylates
How are kinases classified?
by the amino acid residue they phosphorylate
(i.e. Set and Thr or Tyr)
based on activating stimulus / receptor
substrate protein
Cyclin
Best- phylogenetic
How does kinase catalyze a phosphorylation reaction?
positioning reaction partner (hydroxyl and gamma-phospate of ATP together)
What happens in the closed conformation of the glycine rich loop?
gamma-phosphate of ATP in correct position for phosphorylation (fast reaction)
What happens in the open conformation of the glycine rich loop?
It allows for exchange of ADP for ATP
=> kinase activity requires alternating closed and open confirmations
Which form of the kinase is more suited for specific inhibition? (active or inactive)
Inactive -> many ways to distort conformation and prevent activity -> lends itself to high specificity
Active is bad because highly conserved -> low specificity
Can also uses pseudo substrate
Give an example of upstream Kinase regulation
MAP kinase cascade
mitogen activated protein
What to CaMKII and calcineurin mediate?
long term potentiation and long term depression of synaptic strength
- espcially important in learning and memory
What are some clinical kinase inhibitors?
cyclosporin and rapamycin -> immuno suppreressants
Gleevac -> therapy of chronic myeloid leukemia
How does phosphorylation change the character of a protein?
nucleophilic attack at hydroxyl group
- makes more - charge
Which is more regulated: kinases or phosphatases?
Kinase
Phosphatase are constiuitievely active
What is the importance of the activation loop?
kinases activated by phosphorylation of residues in this loop
What is the rate limiting step of the kinase reaction?
ADP-> ATP exchange
What areas of the kinase are distorted in the inactive form?
activation loop
C helix
glycine rich loop (stable or open)
ATP binding pocket
