Exam 3 Kaja: Cell Signaling #2 Flashcards
GPCRs structures have ________ transmembrane domain receptors
The two principal signal transduction pathways involving the G protein coupled receptors are________ and ________
GPCRs: 7 transmembrane domain receptors
There are two principal signal transduction pathways involving the G protein coupled receptors: the cAMP signal and the phosphatidylinositol signal pathway
Explain the structure of G protein receptors
G protein coupled receptors have three subunits, alpha, beta and gamma
alpha and gamma are tethered to the plasma membrane
How do GPCRs get activated?
GPCRs get activated by the following mechanism
Normally, GDP is bound and it is inactive
When an extracellular signal binds, it undergoes a conformational change to kick off GDP, allowing GTP to bind to the alpha subunit (activating it)
Explain the N terminal vs C terminal domains of GPCRs
N terminal domain is the place where post translational modifications happen
C terminal domain is where the binding sites are located
What is cAMP?
How is it produced
cAMP is a second messenger protein, involved in signal transduction (intracellular signal for stuff like glucagon and epi that can’t cross the PM)
cAMP is produced by the enzyme adenyl cyclase, which takes ATP and converts it to cAMP
Adenylyl cyclase is controlled by:
Gs which activates it
Gi which inhibits it
Explain how cAMP activates PKA
cAMP binds to the regulatory subunits of PKA, causing a conformational change that activates the catalytic subunits
Those free catalytic subunits can then catalyze the transfer of ATP terminal phosphates to protein substrates such as Serine or Threonine residues
Explain the structure of GPCRs aka how many subunits, what do they do, etc
GPCRs have three subunits, alpha, beta, and gamma
alpha and gamma are thethered to the PM
GDP binds to the alpha subunit in the inactive form
N terminal troups are where post translational modification happens
C terminal groups is where stuff binds
cAMP is a ____ messenger
It has a ___ short life
_____ converts ATP to cAMP
cAMP is a second messenger
It has a rapid short life, making it unstable
adenylyl cylase converts ATP to cAMP
adenylyl cyclase is controlled by Gs and Gi
Explain the entire cascade from GPCR activation, to PKA activation to gene transcription via CREB
Signal molecule binds to GPCR
Gs activates adenylyl cyclase, which creates cAMP
That cAMP will bind to and activate PKA
PKA catalytic subunits will enter the nucleus and activate/phosphorylate CREB
CREB will then bind to CBP before binding onto the DNA gene section called CRE
Phospholipase C - beta does what to intracellular calcium levels
INCREASES
Explain how PI turns into PIP2
PI ——- (PI kinase)—> PIP4——-(PIP kinase)—–> PIP2
What does phospholipase C beta do/
Phospholipase C-Beta hydrolyzes PIP2 into to parts
DAG (which stays tethered to the PM and activates PKC)
IP3 which then binds to calcium receptors on organelles and increases intracellular calcium
_____ activates phospholipase C beta
which G protein activates phospholipase C beta
G q activates phospholipase C beta
which hydrolyzes PIP2 into DAG and IP3
Calmodulin is a calcium ____ and a signal ____
Calmodulin can bind up to ___ calcium ion
Calmodulin is a calcium sensor and a signal transducer
Calmodulin can bind up to four calcium ions
_____ are serine/threonine protein kinases that are regulated by calcium-calmodulin
Explain the mechanism of their activation/deactivation
CAMKIIs are serine/threonine protein kinases that are regulated by calcium calmodulin
CAMKII is in its inactive form, it binds to calcium-calmodulin which activates it, but more importantly it undergoes autophosphorylation upon binding calcium calmodulin to fully activate itself
The calcium-calmodulin falls off CAMKII, and it is still activated a little. It is not fully inactivated until dephosphorylated by protein phosphatase
