cell signaling Flashcards
(41 cards)
Type of signaling
regulatory signals that originate from conditions within the cell.
communication signals that occur between two neighboring cells.
Response to extracellular regulatory signals that are generated to coordinate metabolic activities and other activities essential for the development and survival of organisms.
model for initiating a cellular response to an extracellular signal
- Unoccupied receptor does not interact with G(s) protein.
- Occupied receptor changes shape and interacts with G(s) protein. G(s) protein releases GDP and binds GTP.
- Alpha subunit of G(s) protein dissociates and activates adenylyl cyclase
- When hormone is no longer present, the receptor reverts to resting state. GTP on the alpha subunit is hydrolyzed to GDP, and adenylyl cyclase is deactivated
What is an important receptor in pharmacology?
G-protein coupled receptors
G-protein coupled receptors
a family of integral membrane cell surface receptors
What are G-proteins characterized by?
- an extracellular ligand-binding domain
- seven transmembrane spanning domains
- a cytosolic G-protein activation domain
G-protein coupled receptors and ligands
bind to specific ligand. conformational changes due to ligand binding are transmitted to the interior of the cell.
Beta and Gamma subunits of the G-protein
act as membrane localizes docking site for the inactive alpha subunit. anchor for alpha
alpha subunit
- binds guanosine nucleotides (GTP/GDP)
1. the inherent ability to hydrolyze GTP to GDP, this is what turns it off.
depending on its activation state, the alpha subunit can interact with..
a specific activated GPCR or adenylyl cyclase
What determines if a g-protein functions to stimulate (Gs) or inhibit (Gi) adenylyl cyclase?
which family of G protein is linked to a GPCR in a cell type
Adenylyl Cyclase
integral membrane enzyme. Enzymatic activity can be stimulated or inhibited by several different proteins, enzymatically utilizes energy from hydrolysis of ATP->AMP + PPi to form cAMP. Generated cAMP quickly
cAMP
second messenger produced by adenylyl cyclase.
What is the target of cAMP
family of enzymes called protein kinases
Protein Kinase A
2 regulatory subunits, 2 catalytic subunits
Catalytic subunits can phosphorylate intracellular effectors.
How does cAMP and protein kinase A work together?
cAMP docks with the protein kinase A regulatory cAMP binding sites, and the protein kinase A catalytic subunits are released.
What do active protein kinase A catalytic subunits do?
phosphorylate target proteins and enzymes to elicit the function of intracellular effectors driven by extracellular signals
intracellular effectors
ion channels, enzymes, DNA binding proteins.
Phosphorylation
can positively or negatively affect the activity of an intracellular effector. It does NOT always turn something on.
protein phosphatases
enzymes that hydrolytically cleave phosphate esters and thus remove/dephosphorylate effector proteins that are phosphorylated by protein kinases
Which amino acids can be phosphorylated
Serine, threonine, tyrosine. they contain an -OH functional group
cAMP phosphodiesterase
is an enzyme that rapidly converts cAMP to 5’-AMP (NOT a signaling molecule)
Disruption of normal adenylyl cyclase activity
A1 interacts with ADP-ribosylation factors, which catalyzes ADP-ribosylation of G alpha so it can never turn off
What is the regulation pathway for intermediary metabolism?
inositol triphosphate and Diacylglycerol signaling
phospholipase C
membrane localized, cleaves lipid bilayer PIP2-IP3 and DAG