__________ receptors convert chemical signals into electrical ones.
Ion channel-linked receptors
Which compound does PKA phosphorylate in the nucleus and what affect does this have?
CREB. CREB binds the target gene which leads to an increase in transcription, followed by translation.
Inositol Phospholipid Pathway
- Signaling molecule binds to a G-protein linked receptor
- G-protein alpha subunit activated
- The alpha subunit activates a phospholipase
- Phospholipase breaks down Pl 4,5-bisphosphate
- The break down of Pl 4,5-bisphosphate results diacylglycerol and IP3
- IP3 will bind to IP3 receptors on the ER membrane
- Calcium released
- Calcium can activate protein kinase C
- Protein kinase C interacts with diacylglycerol which will result in further downstream affects.
A receptor signal molecule that is activated by cleavage?
Notch
What occurs in primary transduction? What steps follow?
The transmembrane protein binds the ligand
A number of intracellular relays can occur so that signal can be modified, amplified, and divered to multiple targets.
How is the alpha subunit of the G-protein inactivated?
The hydrolysis of the GTP by the alpha subunit inactivates this subunit and causes it to dissociate from the target protein
Examples of Small Signaling Molecules that Bind to Nuclear Receptors
Cortisol
Estradiol
Testosterone
Thyroxine
Vitamin D
Retinoic acid
What component downregulated the alpha subunits GTPase activity? What affect does this have?
GTP gamma S; helps the alpha subunit to remain active for a very long time
Bifurcation proteins
Split the cell into 2 signaling pathways
________ and ________ depend on G-protein-linked receptors that regulate cyclic-nucleotide- gated ion channels.
Smell; vision
Example of a metabotropic recepter pathway
- The Metabotropic receptor binds to the G-protein
- Adenylate cyclase is activated
- cAMP is activated
- Protein Kinase A is activated
- The channel will close and no potassium will be able to exit the cell
* Indirect affect
In the intracellular pathway, in what way are the metabolic enzyme, gene regulatory protein, and cytoskeletal protein affected by the cascade?
Metabolic emzyme: Altered metabolism
Gene regulatory protein: Altered gene expression
Cytoskeletal protein: Altered shape or movement
How many subunits does an inactive protein kinase A have?
4 (2 regulatory and 2 catalytic)
What happens to neurotransmitters once they are released into the synpatic cleft and bind to the receptor?
The neurotransmitters are broken down by enzymes found in the synapse. They are then taken up by glia cells or recycled back intot he nerve cell
Adaptor protein
Link one signal pathway to another signal pathway
What does PDGF, FGF, and NGF stand for?
Platelet derived growth factor receptor, fibroblast growth factor, and nerve growth factor
What happens in the cAMP pathway?
cAMP acts on the protein kinase A
Once cAMP binds to PKA, the subunits break up and you get the active PKA catalytic subunits
Intracellular signaling proteins that act as molecular switches
Signaling by Phosphorylation
Signaling by GTP-binding protein
Scaffold proteins
Combine multiple signal proteins together forming a complex
Which type of channels found in gap junctions allow for bidirectional flow? What type of response does this allow for?
Connexon; Fast
What happens in intracellular signaling?
Small hydrophobic molecules cross the membrane and float into the nucleus, where they bind to the intracellular recptors and can cuase changes to gene transcription
__________ make the effects of PKA and other protein kinases transitory.
Protein phosphatases
Enzyme- linked Cell-Surface Receptors are activated by ___________
Growth factors
____________ is a signaling molecule that can activate both ionotropic and metabotropic receptors
Glutamate
Enzyme-linked Receptors (Mechanism)
- Dimerize
- Activate other enzymes
A cell is dependent on multiple extracellular signals that tell it whether to:
Survive
Divide
Differentiate
Die
G-protein linked Receptors (Mechanism). Type of receptor? Type of protein?
- Signal molecule binds receptor
- The receptor activates a G-protein that is also sitting in the membrane
- The G- protein gets activated and splits into two components (alpha and beta-gamma)
- The G-protein can activate other enzymes that are sitting on the enzyme
- The G protein can have kinase activity and phosphoylate/ activate other proteins
Metabotropic Receptor
Transmembrane protein
Messender proteins
Carry signal from one part of the cell to another
What affect does Cholera Toxin have in cAMP, by what mechanism?
Cholera Toxin prevents the alpha subunit from being hydrolyzed by the phosphate , so the alpha subunit will remain in its active form and stimulate adenylyl cyclase indefinitely. This will result in prolonged, elevated cAMP levels, which can result in a large influx of chloride and water in the gut. Final product is severe diarrhea.
Which has greater specificity endocrine signaling or synaptic signaling?
Synaptic signaling
Ion channel linked receptor mechanism. What type of receptor? What type of protein?
- Signal molecule binds the receptor
- The receptor undergoes a conformational change into an ion channel
- Specific ions are able to pass into and out of the the channel
Ionoctropic receptors
Transmembrane protein
Signaling by Phosphorylation
Types
When is it active, when is it not?
Types: Serine/ Threonine kinases, Tyrosine kinases
Active when phosphorylated
Inactive when dephosphorylated
What is the difference between ionotropic and metabotropic receptors?
Ionotropic receptors have a direct affect on the ion channel and metabotropic receptors do not.
_________ activates adenylyl cyclase.
Stimulatory G protein (Gs)
How does cortisol affect transcription? (mechanism)
- Cortisol crosses the membrane
- Once cortisol is near the receptor, the receptor undergoes a conformational change, which activated it
- Cortisol binds the receptor
- Cortisol-receptor complex travels the nucleus and binds to regulatory region of the targe gene
- Activates transcription
Which type of Cell-Surface Receptor has slow and direct rapid responses?
Enzyme linked
Latent regulatory proteins go to the __________
Nucleus
What response does acetylcholine induce in the heart muscle, salivary gland cell and skeletal muscle?
Heart muscle: Decreased rate and force of contraction
Salivary gland: Secretion
Skeletal muscle: Contraction
_________ inhibits adenylyl cyclase.
Inhibitory G protein (Gi)
Singling by GTP-Binding Protein
Active when GTP is bound and inactive when GDP is bound
Three types of cell-surface receptors
Ion- channel linked receptors
G-protein linked receptors
Enzyme-Linked Receptors
What component can enhance the binding of the target protein? What other roles does this component have?
RGS; Plays a role in shutting off the G-protein mediated response
In a group of identical signaling cells, each cell receives a strong ____________ signal. Why?
Autocrine. Due and increase in conentration
What gas can cross the plasma membrane and activate the intracellular enzymes directly?
Nitric Oxide
What happens in extracellular signaling?
A hydrophilic signal molecule bind to a cell-surface receptor, which can lead to an intracellular cascade or secondary messsenger cascade
In which type of signaling does the signal last longer, sypaptic or endocrine?
Endocrine becuase the signaling mechanism takes time.
How do hydrophobic molecules travel through the blood stream?
On carrier proteins
Pertussis Toxin
Causes whopping cough. It acts on the inhibitory G protein which will result in an inactive alpha subunit, which will result in adenylyl cyclase not being activated.
Adenylyl cyclase makes cAMP out of _________
ATP
What happens after the alpha subunit of the G-protein complex is inactivated?
It reassembles with the beta-gamma subunit to reform and inactive G-protein
Relay proteins
Signal being communicated
Transducer proteins
proteins that receive and help process information so that proper action by the cell ensues.