FOM 7.2.2 Flashcards
What are the key characteristics of second messengers?
non-protein, rapidly prod/mobilized, diffusible, bind 2nd messenger effectors
What are the six prominent 2nd messengers?
cAMP, cGMP, Ca, diacylglycerol, IP3, NO
What are the four types of critical components of 2nd messenger signaling?
Activators (GPCR, kinase, 2nd messenger)
Produce/Mobilize 2nd messenger (cyclases, phospholipases, channels, NOS)
2nd messenger Targets (kinases, channels)
Downregulation (phosphodiesterases, channels, metabolic enzymes)
What two of the most common G protein effector molecules?
Adenylate cyclase (AC) and Phospholipase C (PLC)
When the G alpha s (GTP) subunit binds adenylate cyclase, what is rapidly produced by AC?
cAMP
What is the primary target of cAMP?
PKA, protein kinase A
Describe how cAMP activates PKA.
PKA actually consists of 2 regulatory subunits (R) bound to 2 catalytic subunits (C). Binding of cAMP to the regulatory subunits releases the catalytic subunits, which are now active.
What are the 4 phosphorylation targets of PKA?
1) phosphorylation of GPCRs leads to heterologous desensitization
2) phosphorylation of metabolic enzymes
3) cAMP response element-binding proteins (CREB) are transcription factors
4) conductance regulator channel (CFTR)
Describe how cholera toxin effects the second messenger pathway.
Individuals with cholera exhibit sustained production of cAMP (ADP ribosylation of GalphaS ) in intestinal cells. This leads to unregulated PKA activity. PKA phosphorylates and activates the CFTR channel, ultimately leading to secretion of salt into the intestinal lumen, followed by osmosis of water. This results in massive diarrhea and dehydration and can even lead to death.
What is the end result of the activating mutation in the Luteinizing hormone (LH) receptor? What is the end result of the deactivating mutation in the Luteinizing hormone (LH) receptor?
Activating: precocious testosterone prod -> precocious puberty (as early as age 3)
Deactivating: pseudohermaphroditism
What is the role G alpha protein?
After dissociation with it affects adenylate cyclase and phospholipase C
Upon activation what is the role of adenylate cyclase?
It converts ATP to cAMP
What is adenylate cyclase inactivated by?
G alpha i
What is the basic activation sequence of cAMP signaling?
After signaling through GPCR the G alpha subunit is activated. The alpha subunit then goes and activates adenylate cyclase. Which then turns ATP to cAMP. Increased intracellular cAMP leads to activation of PKA by dissociating it from its regulatory subunit. PKA will go and do a number of processes.
What are some effects of activated PKA?
Phosphorylation of GPCR leading to desensitization. Increased blood glucose levels. Activating CREB which can lead transcription of genes. Targeting CFTR to transport salt across the membrane of the intestine.