Signal Transduction Pathway (PKC) Flashcards
What are the 3 classes of PKC isoforms?
- cPKC (conventional)
- nPKC (novel)
- aPKC (atypical)
How are the isoforms of PKC activated?
- cPKC activated by Ca2+, DAG, Ps
- nPKC activated by DAG, Ps
- aPKC activated by Ps
What is the difference in domain structure of cPKC, nPKC and aPKC?
- Switched pseudo c1 domain for nPKC as does not need Ca2+ (inactive for Ca2+ binding)
What do the 2 regulatory domains bind?
C1 - DAG bind
C2 - Ca2+ bind
What are the 2 domains in PKC and what do they bind?
- Regulatory domain (DAG/Ca2+)
- Hinge region
- Catalytic domain (ATP/Substrate)
What are the roles of PKC?
- signal transduction
- cell proliferation
- apoptosis
What does DAG stand for?
Diacylglycerol
What do the 2 catalytic domains bind?
C3- ATP bind
C4 - Substrate bind
What does the hinge region do?
Connects regulatory and catalytic domain
Contains pseudo substrate sequence that inhibits kinase activity
Where is the active site of kinase?
Catalytic domain
What happens at the active site of kinase?
P group from ATP -> serine / threonine on target proteins
How are aPKC’s activated?
- PB1 domain binds to proteins causing conformation change -> activate kinase
- Phosphorylation of threonine
How is DAG formed for PKC activation?
- PIP2 phosphorylated
- PLC enzyme cleaves PIP2
- DAG + IP3 formed
- PLC is isoform dependent
What are the 5 steps for PKC activation?
- Ligand + GPCR or RTK activates PLC
- PLC cleaves PIP2 -> DAG + IP3
- IP3 binds to receptors on ER releasing Ca2+ into cytoplasm
- Ca2+ influx as higher conc. inside ER than cytosol due to IP3
- PKC activated via Ca2+ and phosphorylates inactive proteins
How can you use IP3 to switch off kinase activation?
- IP3 -> IP2 dephosphorylation
