cell signaling Flashcards
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
IP3
inositol 1,4,5-triphosphate binds ER receptor, releasing Ca2+ from ER to cytosol
PIP2
Phosphatidylinositol 4,5-biphosphate is a membrane phospholipid
Protein Kinase C
major target activated by DAG and Ca2+, functions with Ca2+ to synergystically promote (metabolic) responses by phosphorylating proteins, it is cAMP dependent. What promotes change in cellular program
What ligand stimulate IP3 and DAG signaling
nurotransmitters, hormones, and growth factors
Ca2+ as a signaling molecule in the liver
calcium released from ER, 4 calcium bind to calmodulin, calmodulin-Ca complex results in a conformational change that permits interactions with and activation of enzymes involved in metabolism
coordination of energy metabolism is controlled by
Primary-two peptide hormones-insulin and glucagon
Supporting-two catecholamines-epinephrine and norepinephrine
insulin
a protein hormone that is water soluble
produced in beta cells in the islets of Langerhans in the pancreas
stored in secretory granules
anabolic effector
what does insulin promote
production of glycogen, triacylglycerides, protein
regulation of insulin secretion
beta cell secretion of insulin is coordinated with alpha cell secretion of glucagon
the rate of glucose use by peripheral tissues as a result of insulin secretion is counter balanced by
glucagon release, hepatic glucose production rates
increased insulin secretion from glucose
results in coordinated increase in insulin rate, beta cells produce more insulin, glucagon levels decrease
increased insulin secretion from amino acids
increased amino acid concentration and insulin secretion stimulated, glucagon release is unregulated to compensate for the increased insulin and thus glucose uptake
increased insulin secretion from GI hormones
peptide hormones are released from the small intestine as anticipatory insulin release stimulators in response to food ingestion, insulin secretion is greater when glucose is ingested in contrast to given IV
factors that negatively affect insulin secretion
scarcity of dietary fuels such as glucose and amino acids
Increase in blood levels of epinephrine
Epinephrine release is regulated by the nervous system and is secreted by the adrenal medulla in response to
stress, trauma, extreme exercise
epinephrine directly affects mobilization of
glucose from the liver
fatty acids from adipose tissue
what can override the normal glucose-stimulated release of insulin?
epinephrine
