B2.084 - Cellular Signaling Flashcards
What are the components of G protein coupled receptor signaling
G protein coupled receptors
Heterotrimeric G proteins
Guanine nucleotide (GTP, GDP)
How do you turn on G coupled receptor signaling
Ligands stimulate binding of guanine nucleotide GTP to heterotrimeric G proteins
How do you turnoff G protein coupled receptor signaling
Hydrolysis of GTP to GDP; prevent re-binding of GTP to heterotrimeric G proteins
What are some clinical examples of G protein coupled receptor signaling
Fight or flight response
Beta blockers
Cholera
Jansens metaphysical chondrodysplasia
What are the components of second messenger signaling
Adenylate cyclase, cAMP Calcium ER inositol triphosphate (IP3) DAG Phospholipase
How is second messenger signaling turned on
G protein activation
How is second messenger signaling turned off
Down regulate G protein signaling
Degradation and/or sequestration of second messengers
What are some medical examples of second messenger signaling
Cholera, Cushing’s syndrome
In GPCR signaling a lingand binds and causes
Conformational change in the receptor which translates to the heterotrimer
In GPCR conformational change in the heterotrimer leads to the promotion of
Nucleotide exchange which causes activation
In GPCR nucleotide exchange is followed by what
GTP-alpha and beta gamma subunits dissociate and interact with effector molecules
In GPCR what do the effectors do
Bind active G protein subunits and trigger downstream signaling events
In GPCR signal duration is regulated by what
How long GTP remains bound
What intrinsic factor activity helps regulate how long GTP stays bound
GTPase
Hydrolyzes GTP to GDP
What helps accelerate the desensitization of the G protein?
GTPs activating proteins (GAPs)
Free beta gamma subunits recruit GRKs for what purpose
GRKs phosphorylates only ligand occupied GPCRs
What do phosphorylated GPCRs do?
Recruit and bind arrestins
Phosphorylated arrestin bound GPCRs cant do what
Interact with heterotrimer, the G protein activation cycle is broken
What happens to the Arr bound GPCR
Its internalized and degraded
Or
Dephosphorylated and recycled to the cell surface
How do beta blockers work
They bind norepinephrine and epinephrine, inhibiting the fight or flight response. This lowers blood pressure and has a calming effect
How does vibrio cholerae work
The bacteria targets the small intestines and secretes a toxin that is internalized by the cell.
What is the cholera toxin
An ADP ribosyl transferase that ADP-ribosylates Arg201 of the G alpha subunit.
What ADP ribosylated G alpha subunit cant do what
Hydrolyze GTP, this causes the G protein to be always active.
What is one of the most common G protein effector molecules
Adenylate cyclase
