Signal Transduction Flashcards
What is the most highly regulated ion?
Ca2+
What are the two co-dependent sources of Ca2+ and what is its function?
Blood Ca2+ and Cytosolic Ca2+
Ca2+ homeostasis and 2nd Messenger
Neurotransmitters such as _____ stimulate muscle contraction.
Acetylcholine
Metabolites include ________. It does _____________ to a receptor
Glucose, does NOT BIND to a receptor. Rather, it stimulates insulin release from the pancreas.
__________ produces ATP which regulates ____ and ________.
Glycolysis, ion channels and insulin release
Hormones such as _______ and ______ regulate________.
Glucagon, Insulin
Regulate metabolic homeostasis
Growth Factors include _____.
Epidermal Growth Factor
What are the 6 types of Chemical Messengers?
Ions
Neurotransmitters
Eicosanoids
Metabolites
Hormones
Growth Factors
Eicosanoids are responsible for _____. Examples include ______.
Response to injury
PGs, TXA, Leukotrienes
What chemical messengers regulate glucose? What is their function ?
Insulin tells our tissues we have been fed with glucose.
Glucagon and epinephrine signals tell us that we are not fed and glucose is needed.
- The ______ puts out glucose when we are not fed.
- _____ and _______ tell the ________ to release _______.
- ________ lowers _______ by stimulating ______ in ______.
liver
Glucagon and Epinephrine, liver to release glucose to blood
Insulin, blood glucose, uptake in adipose and muscle cells
Which cells store glucose?
Adipose and Muscle Cells
How do chemical messengers signal changes in the cell?
Cells secrete chemical messengers in response to stimulus which bind to specific receptors on target cell which can be on the cell or inside it.
The receptor binding elicits a response which allows the messenger to diffuse or transport through blood.
How do 2nd messengers affect the process of signal changes in cells?
The first chemical messenger secreted in response to stimulus binds to a cell SURFACE receptor.
The second messenger is generated in response to the first messenger.
Changes in the 2nd messenger levels lead to changes in protein activity in cell.
In secondary messenger systems, _________ in 2nd messenger _____ is what leads to changes in _______.
This means 2nd messengers are present at ___ levels in cells so that ______ changes can have a big effect.
changes, levels
protein activity in cells
low levels, small
What are the three classes of cell surface receptors?
Ion Channels
Tyrosine Kinase Receptors
G-Protein Couples Receptors
What are 3 examples of ion channels?
Cytosolic Ca2+
Membrane Potential
Insulin Release
What are 3 examples of tyrosine kinase receptors?
Insulin
EGF
GH, PRL associated JAK kinases (don’t need to know)
What are 3 examples of G-protein coupled receptors?
Epinephrine, Glucagon
cAMP ( IP3/DAG/CA2+)
Cytosolic Ca2+ ________ in Cell
In a resting cell, the Ca2+ level is ______ in the cytosol. Ca2+ channels allow Ca2+ ions to diffuse _________ and through the ________.
This process is controlled by _______ in the ______.
Ion Channel
In a resting cell, the Ca2+ level is higher in the cytosol. Ca2+ channels allow Ca2+ ions to diffuse down its electrochemical gradient and through the cell membrane.
Ca2+-atpases in the plasma membrane.
Cytosolic Ca2+ ________ in Cytosol
- Cytosolic Ca2+ is normally_______. The plasma membrane potential ( ____) is ______ or _______-.
- A more _________ membrane potential or ______- increases ______-.
- ________ of the membrane channel causes ______ to open.
- ______ channels allow ______ to flow from _________ to the ______.
Ion Channel
- low, Vm
negative/ polarized - positive , depolarization
cell activity - Depolarization, Ca2+
- Ca2+ , Ca2+ to flow from outside the cell into the cytosol.
While ______ directly regulate cystolic Ca2+, ____ channels indirectly regulate Ca2+ channels by __________.
Ca2+
K+, changing Vm (membrane potential)
When K+ channels are open, the membrane potential _____________ because ______. This _________ Ca2+ channels so that less _______ enters the _____. Remember! Membrane potential is normally ______.
When K+ channels are closed, the membrane potential _____________. This _________ Ca2+ channels so that more_______ enters the _____.
is polarized because K+ ions are leaving the cell.
closes, less Ca2+ enters the cell
Membrane potential is normally negative or polarized.
is depolarized
opens, more Ca2+ enters the cytosol
K+ channels can influence ______.
Certain K+ channels called _______ can be influenced BY ______. It couples ______ to ________ in _________.
When ______ in the cell is low, the membrane potential is ________. This means the ________ are _______ so that _________.
When ______ in the cell is high, the membrane potential is ________. This means the ________ are _______ so that _________.
ATP
ATP Gated Potassium Channels (Katp) can be influced by ATP levels.
It couples high blood glucose to insulin release in pancreatic beta cells.
When ATP in the cell is low, the membrane potential is polarized. Katp channels are open so less Ca2+ enters the cytosol.
When ATP in the cell is high, the membrane potential is depolarized. Katp channels are closed so more Ca2+ enters the cytosol.
Describe insulin release from pancreatic beta cells as regulated by Katp and Cav channels.
- When blood glucose levels rise, pancreatic beta cells take up glucose through transporters.
- Inside the beta cell, glucose is metabolized to produce ATP.
- Increased ATP binds to KATP channels, causing them to close and the membrane to depolarize resulting in a less negative membrane potential.
4.Depolarization of the membrane opens voltage-gated calcium channels (Cav).
- Calcium ions flow into the cell through the open Cav channels.
- Elevated intracellular calcium concentration triggers the fusion of insulin vesicles with the cell membrane, releasing insulin into the bloodstream.
_________ of the membrane potential due to _________ is what triggers the _______ of insulin.
Depolarization of the membrane potential due to an increase in ATP from glucose that causes KATP to shut down is what triggers the release of insulin.
Glucose enters _______ via ___________ which is a _______.
_______ generated from _____ closes _________.
Reduced _________ causes the membrane to _________. This __________.
Increased ____ stimulates _______ of.
B-cells , GLUT2, transporters
ATP, catabolism, KATP
K+ efflux, depolarize. This opens Cav channels
Increased cytosolic Ca2+, the exocytosis of insulin containing vesicles.
Ca2+ channels are triggered to open by the ______________ of the membrane potential.
depolarization.
________ bind GTP/GDP. ______ undergo conformational changes in response to ________.
G proteins are also enzymes called _________ which make the protein _________ because they ______________
What helps release GDP?
G-Proteins. G-Proteins, protein-protein interaction.
GTPases make the protein inactive because they hydrolyze GTP to GDP.
Nucleotide Release Factor
What are the two families of G-proteins?
Heterotrimeric and Small GTPases
What are heterotrimeric G-proteins subunit types?
Alpha s
Alpha i
Alpha q
What are the Small GTPases
Ras
Rho
Rab
AlphaS is a ________ that is responsible for _______.
heterotrimeric G-protein subunit type that is responsible for stimulating adenylate cyclase to increase CAMP
AlphaI is a ________ that is responsible for _______.
heterotrimeric G-protein subunit type that is responsible for inhibiting adenylate cyclase to decrease CAMP
Alphaq is a ________ that is responsible for _______.
heterotrimeric G-protein subunit type that stimulates phospholipase C to increase IP3/DAG/CA2+
Which heterotrimeric G-protein subunit is also a GTPase.
Alpha
Heterotrimeric G-proteins are associated with _______.
G-protein couples receptors
cAMP/ IP3/ DAG and Ca2+ are all ______.
G-proteins
Ras is a ______ that ___________.
Small GTPase, controls cell growth through Serine and threonine protein kinases
Rho is a ______ that _______.
Small GTPase that reorganizes cytoskeleton through
Serine and threonine protein kinases
Rab is a _______ and plays a ______.
Small GTPase, plays a role in key secretory and endocytotic pathways.
Kinases ______ while phosphatases ________.
Add Phosphates, Remove phosphates
GPCR and 2nd Messenger systems.
Heterotrimeric G-proteins contains __________ subunits. When ______ bound to _____ the protein is inactive. The activation via ______ causes the ____ to dissociate from the ________. This can cause __________.
The active _____ subunit binds to ____ to change its activity or _______.
AKA; 2nd messengers can regulate cellular activity by regulating ________.
3 subunits ( alpha beta gamma)
the alpha subunit is bound to a GDP, the protein is inactive.
When bound to GTP, the alpha subunit dissociates from the beta and gamma subunits.
Alteration in the activity of enzymes and ion channels.
The active alpha subunit binds to target protein and changes its activity to increase or decrease a second messenger.
Protein kinases (GDP to GTP)
cAMP 2nd Messenger System
- ________ converts ATP to _______.
- Ga-GTP targets ________. If its Gas, AC will _________ while Gai will __________ it.
- _______ activates _________.
- _______ degrades ________ into __________.
- Adenylyl cyclase converts ATP into cAMP.
- Ga-GTP targets AC. activate/ inactivate
- cAMP activates Protein Kinase A.
- cAMP phosphodiesterase degrades cAMP into AMP
What are key features of 2nd Messenger systems?
- Specificity
- Amplification
- Augmentation - Different hormones activate the same system
- Rapid Signal Termination by enzymes and transporters
Specificity
Different _______ interact with different G-proteins. Binding with _______, _____ and ______ all has different effects.
GPCRS
Alphas, Alphai,Alphaq subunits of the heterotrimeric G-protein.
Gai
inhibits AC which decreases cAMP and makes PKA less active
Gaq
increases IP3/DAG/Ca2+ and Protein Kinase C is activated
Gas
activates AC which increases cAMP and makes PKA active.
Specificity
The _____ receptor can interact with Gas which increases _________ in both _____ and _______.
In the liver, this ______ while in the adipose tissue it _____.
Glucagon, cAMP in both liver and adipose tissue.
stimulates pathways to increase glucose output.
stimulates lipolysis to release fatty acids and glycerol
Specificity
Epinephrine is a _____ and has receptors in _______.
Where does it bind to and what are the effects
stress hormone, many cells
- Vascular Smooth Muscle and Heart to increase HR and BP
- Liver to increase glucose output
- Skeletal muscle to increase ATP production for contraction
________ is produced by the ______ and stimulates the ______ to release glucose.
Glucagon is produced by the pancreas and stimulates the liver.
When glucose is low in blood, glucagon increases to stimulate release of glucose by liver into blood via gluconeogenesis and glyconeogenesis.
Augementation
Both _______ and ____ can both stimulate cAMP in the ____.
Glucagon and epinephrine can both stimulate cAMP in the liver
__________ is a tyrosine kinase receptor.
Insulin Receptor
- Insulin binding induces ______ of __________ on the receptor and ________.
- Activates insulin receptor __________ proceeds to _______ on _________ which
phosphorylation of tyrosine residues on the receptors and activates its tyrosine kinase
phosphorylate tyrosine residues on insulin receptor substrate which activates a protein kinase cascade.
How do insulin pathways regulate cell growth?
They stimulate cell growth via a mitogen activity which is stimulated by MAP kinase activity.
What is a mitogen?
Causes cells to divide
What is MAP kinase?
Mitogen Activated Protein Kinases
How do insulin pathways regulate fuel metabolism?
Insulin binds to insulin receptors, which initiates a signaling cascade that activates the PI3K/Akt pathway.
This pathway stimulates glucose uptake by increasing GLUT4 trafficking to the cell surface in muscle in adipose tissue and increases synthesis of glycogen,lipid and proteins.
It inhibits the release of glucose from the liver.
AKT is a _____ which regulates _______. It _________ and activates ___________ which _______.
protein kinase, phosphatase -1
phosphorylates and activates phosphatase-1. This reverse the effects of PKA on liver glucose output.
Remember PKA increases glucose output from the liver.
Growth Factor Receptor Tyrosine Kinases Activate __________.
- __ binding stimulates __________ and _______.
- Recruitment of ____ and _______ which are _______ activate ________.
- _________ binds to ____ which is a _______ and initiates the _____ to _________
Ras G-Proteins
- EGF binding stimulates receptor dimerization and autophosphorylation
- Recruitment of adaptor proteins Grb2 and SoS activate Ras.
- Ras-GTP binds to Raf which is a mitogen activating protein kinase and initiates the MAP kinase cascade to stimulate cell growth.
Mutations in Ras can _________ GTPase activity thus locking the Ras in a _______ state causing the ________ to be ____.
This increases________ and can cause _______.
abolish GTPase activity thus locking Ras in a GTP bound state cause the MAP kinase cascade to always be on.
This increases cell proliferation at a rate independent of the growth factor and can cause cancer.
Over-expression of ________ and _______ is associated with Oral Cancer
EGFR and Ras
