Ser/Thr Kinases Flashcards
Where are beta adrenergic receptors found?
In the heart
When beta adrenergic receptors are activated what signalling cascade is activated?
- cAMP activates PKA
- PKA phophorylates and increases probability L-type calcium channel is in open state
When PKA is activated in cardiac muscle what effect does it have on contraction?
Increases strength of contraction by increasing Ca2+ influx through calcium channel
What are the long term effects of PKA?
PKA phosphorylates CREB which is activated and recruits CREB binding protein, this is involved in upregulating metabolic processes and increasing muscle mass
What effect does activation of alpha adrenergic receptors have?
Rapid mobilisation of Ca2+ down concentration gradient from ER into cytoplasm
What protein sense Ca2+?
Calmodulin
How does activation of alpha adrenergic receptors regulate contraction of muscle?
- Influx of Ca2+ binds to troponin
- Troponin binds to filamentous actin and stops productive interaction with myosin so can’t get muscle contraction
- When Ca2+ binds to troponin inhibition relieved and actin and myosin can interact
How does the specific camkinase MLCK work?
- Ca2+ is released and binds to calmodulinand active complex binds to MLCKand activates the kinase which can phosphorylate myosin’s light chain which can trigger contraction in smooth muscle
How is PKC inhibited?
- It is autoinhibited
- Pseudosubstrate interacts with active site and blocks it, inhibiting function
- In absence of signal PKA adopts an inhibited hairpin-like conformation
How is PKC autoinhibition relieved?
- when Ca2+ and DAG are present they can bind to PKC domain with high affinity
- This releases the autoinhibition
Where does Ca2+ bind on PKC?
C2
Where does DAG bind on PKC?
C1
