Flashcards in 2nd messengers Deck (37):
How many isoforms of Adenylyl cyclase (AC) exist?
All 9 form of (AC) are stimulated by?
Which form are inhibited by Galpha(i)
V and VI
Does the Gbetagamma dimer stimulate or inhibit AC?
Guanylyl cyclase make which 2nd messenger?
Differentiate between type 1 and type 2 guanylyl cyclase
type 1 is membrane bound, has a ligand binding site.
Type 2 is soluble.
What degrades cAMP and cGMP. Is it selective?
Phosphodiesterase (PDEs) degrades them into 5' AMP and GMP, inactive.
Some PDEs degrade both cAMP and cGMP, others degrade one or the other.
Which sensory system uses PDEs?
PDE2 breaks down cAMP. PDE2 is activated by cGMP.
Explain serotonin signaling mechanism.
Binds to a GPCR, which causes Galpha(s) to activate AC which in turns makes cAMP rise, until phosphodiesterase gets it all locked down and under control again.
Explain protein kinase A (PKA) regulation.
PKA is made of four subunits. two regulatory, which bind cAMP, and two catalytic. Catalytic are kept inactive until cAMP binds and allows them to disassociate from their regulatory domains.
Explain possible longterm and shortterm affects of PKAs.
PKA can activate through phosphorylation proteins in the cytosol causing a short term affect.
PKA can also activate KREB the same way, which will bind a CREB-binding protein and then activate gene transcription.
What does CREB stand for?
cAMP response element binding.
What is a cAMP response element?
It is a stretch of dna in the promoter region which activates a gene when bound to by a CAMP with cAMP binding protein.
How many phosphoinositides are there?
PI-4-5-P2 is what makes IP3 and DAG.
What does IP3 do?
opens Endoplasmic Reticulum Calcium channels.
What does DAG do?
What does PI3K do? What does it stand for?
It adds a phosphate at position three.
Phosphoinositol 3 kinase
What are pleckstrin homology domains?
they are regions which bind PI(3,4,5)P3. They allow proteins to use phosphorylated phosphoinositols as a docking site.
What is the advantage of docking sites?
It can bring proteins which need to phosphorylate each other into close proximity. like with BTK and PLC-gamma.
Explain activation of B-Cells
Activated antigen receptor draws in PI3K.
PI3K takes PI(4,5)P2 --> PI(3,4,5)P3. Which acts as a docking site for BTK (Bruton's tyrosine kinase) and PLC-gamma (phospholipase C gamma).
PLC gamma cuts PI(4,5)P2. into DAG and IP3. Which signal for the B-lymphocyte to proliferate.
What happens if the PH domain of BTK is mutated.
BTK cannot bind to its docking site. PLCgamma is not phosphorylated doesn't cut PI(4,5)P2 --> IP3 and DAG.
Person is immunocompromised.
Are PI(3,4)P2 and PI(3,4,5)P2 cleaved by phospholipase C?
NO!!! Just PI(4,5)P2.
If PI(3,4)P2 and PI(3,4,5)P2 are not cleaved by a phospholipase, how are they inactivated?
Inositol phospholipid phosphatase can take those phosphates off whenever he feels like it!
Compare the types of PI3K
One is activated by receptor tyrosine kinases, it is made of a regulatory and catalytic subunit.
The other is activated by the Gbetagamma subunit. It has a different regulatory subunit an but a similar catalytic subunit.
What other means exists to activate PI3Ks?
The monomeric RAS G-Protein in its active state (RAS GTP) can bind to and directly activate the catalytic subunit of PI3K.
What task does DAG perform?
It activates types of PKC. DAG--> arachodonic --> prostaglandins and eicosanoids mediating inflamatory response.
Where is phosphatidylinositol located at?
In the cytosolic leaflet of the PM.
Add phosphates to positions on the inositol ring.
Phopholipase C-beta is activated by what?
GPCRs coupled to Galpha(q/11)
PLC beta does what?
cleaves PIP2 --> DAG and IP3.
ER/SR ionotropic receptors for Ca2+
What are Ca2+ ATPases used for?
They resequester Ca2+ into the ER/SR. They are a pump.
How does the sperm cause a Ca2+ propagation?
Thought to bring its on phospholipase C into the egg.
What about Na+ driven Ca2+ exchangers?
They send Ca2+ out of the cell.
What is the function of Calcium binding molecules?
They bind Ca2+ buffering it.
Ca2+ spikes similar to Na channels in a ...
... action potential. These spikes are called calcium transients.