Cell Signalling Flashcards
What are the 6 steps to cell communication?
Synthesis of signal Release of signal Transport of signal Detection of signal Change in the cellular process Removal of signal
What are the different types of cell signaling?
Direct contact Paracrine signaling Autocrine signaling Endocrine signaling Synaptic signaling
What is direct contact signaling?
Transferring a signal molecule across a gap junction between neighboring cells
What is paracrine signaling?
A cell produces a signal to induce changes in nearby cells
What is autocrine signalling?
A cell produces a signal that induces a change on the same cell
What is endocrine signaling?
A cell produces a signaling molecule which travels through the bloodstream to bind to receptors on a distant cell
What is synaptic signalling?
A cell produces a signal to induce a change in nearby cells, passing the signal through a synapse
What occurs in a cell after a signal arrives?
The ligand binds to the receptor, inducing a single response or multiple responses
What is phosphorylation?
The addition of a phosphate to an organic compound
What is a protein kinase?
An enzyme that phosphorylates proteins
How does a protein kinase carry out its function?
It removes a phosphate from ATP and then gives that phosphate to a protein
What is a protein phosphatase?
An enzyme that dephosphorylates a protein
What are the different types of cell surface receptors?
Chemically gated ion channels
Enzymatic receptors
G-protein coupled receptors
How does a chemically gated ion channel work?
A ligand binds to the channel, opening it. This allows the movement and transport of ions through the channel
How do enzymatic receptors work?
The binding of an extracellular ligand cause intracellular enzymatic activity
How do G-protein coupled receptors work?
A ligand binds to the receptor which stimulates the conversion GDP to GTP which activates an enzyme or ion channel
How are intracellular receptors reached?
A ligand must be able pass through the cell membrane to reach these
Then ligand can then bind to recpetor in the cytoplasm or nucleus
Why can a steriod activate intracellular receptors?
As steriods are lipid soluble meaning they can pass through the membrane into the cell
What are steriod receptors and what do they do?
Steriod receptors are intracellular receptors that initiate signal transduction for steroid hormones which changes gene expression
What are the binding domains of a steroid receptor?
Hormone-binding domain
DNA binding domain
What occurs at the hormone-binding domain of steroid receptors?
Forms a hormone receptor complex
Initiates signal transduction which leads to a change in gene expression
What occurs at the DNA binding domain of steroid receptors?
Once the steriod hormone binds to the receptor, the receptor dimerises and binds to the DNA sequence
-acts as a transcription factor
What are receptor tyrosine kinases (RTK)?
High affinity cell receptors involved in regulating lots of normal cell processes such as the cell cycle, growth, proliferation, metabolism etc
How are receptor tyrosine kinases regulated?
By autophosphorylation
When a ligand binds to the receptor is induces the dimerization of the 2 receptors allowing them to phosphorylate themselves
What is the insulin receptor?
A receptor that insulin binds to when blood glucose is high
Where is insulin made and what does it do?
Insulin is made in the pancreas
Insulin stimulates the formation of glycogen from glucose
What is a glucose transporter?
A membarne protein that facilltates the movement of gluocse across the cell membrane
What occurs when insulin binds to the insulin receptor?
- Glucose transporters stored in membrane vesicles
- When insulin binds to the insulin receptor, glucose transporters move to the cell membrane for movement of glucose ( decreasing blood glucose)
- When insulin levels decrease glucose transporters move back into membrane vesicles
What are docking proteins?
Proteins that dock onto and help other proteins dock onto phosphotyrosines to become phosphorylated
What happens at the glycogen synthase signaling pathway?
- Insulin binds to extracellular domain of receptor
- Causes the autophosphorylation of the intracellular domain
- Insulin response protein (docking protein) binds
- Activates glycogen synthase which converts glucose to glycogen (blood sugar decreases)
What is a kinase cascade?
Where a protein kinases phosphorylates another proetins kinases and that repeates until MAP kinase activated
What is MAP kinase stand for?
Mitogen-activated protein kinase
How could amplification of the kinase cascade or signal occur?
If each enzyme acts on multiple substrates
Therefore large amount of final product, meaning a larger response
What are scaffold proteins?
A large protein that groups together and organises the kinase cascade for ultimate efficiency
What are G-proteins and what do they do?
Family of proteins that act as molecular switches inside cells
-They are heterotrimeric membrane associated proetins that bind GTP
They link the receptor proteins to the effector proteins
What is adrenaline and where is it made?
Made in the adrenal glands
Mediates stress response- mobilisation of energy
Which cells can adrenaline bind to?
Liver cells
Adipose cells
Heart cells
What does adrenaline induce when it binds to recpetors in liver cells?
The breakdown of glycogen
What does adrenaline induce when it binds to recpetors in adipose cells?
Lipid hydroysis
What does adrenaline induce when it binds to recpetors in heart cells?
Increased heart rate
Explain the process that occurs when adrenaline binds to its receptor?
- Adrenaline binds to the G-protein coupled receptor
- Beta and Gamma subunits dissociate from the G-protein
- Allows for conversion of GDP to GTP
- GTP and alpha subunit activate adenylyl cyclase
- Adenylyl cyclase converts ATP into cAMP
- This activates PKA, which activates response proteins to create a cellular response
Explain the self-inactivation of G-protein signaling?
- When G-proteins bound with GDP they are off
- Displacement if GDP by GTP turns it on
- Beta and Gamma subunits dissociate allowing the GTP and alpha to activate adenylyl cyclase
- Once activating adenylyl cyclase it gets dephosphorylated back to GDP
- Allowing beta and gamma subunits to redissociate (turning it off)
What are Beta-adrenergic receptors?
They are a class of G-protein coupled receptors
What does BARK stand for?
Beta-adrenergic protein kinase
What does Barr stand for?
Beta-arrestin
Explain the desensitization of Beta-adrenergic receptors?
- Binding of Epinephrine to Beta-adrenergic receptor triggers dissociation of the beta and gamma subunits of the g protein
- The beta and gamma subunits recruit BARK which phosphorylates the carboxyl terminus of receptor
- Barr binds to the now phosphorylated terminus of the receptor
- Receptor-arrestin complex moves into cell by endocytosis (removing from cell membrane) then Barr dissociates
Explain and example of how G-protein coupled receptors can use other secondary messenger molecules (activating PLC)?
- GTP bound alpha subunit of G protein activates phospholipase C (PLC)
- PLC cleaves PIP2 into IP3 and DAG
- IP3 moves into endoplasmic reticulum, causing calcium ions to move out and activate calcium sensing protiens such as PKC or calmodulin
- DAG also activates PKC (protein kinase C)
Explain how different G proteins can activate the same tranduction pathway in a flight or flight response?
- Adrenaline and Glucagon
- Both initiates the conversion of GDP to GTP, and then ATP to cAMP
- Collectively activating PKA
- Activating phosphorylase kinase
- Activating glycogen phosphorylase which converts glycogen to glucose for mobilization of energy
Give an example of how adrenaline can have different effects on things ?
-Increases the heart rate
- But relaxes the smooth muscle of intestine
(less peristalsis- as we are not interested in digesting food at this point)
Explain how different G proteins have an opposite effect on the same transduction pathway?
- A stimulatory hormone such as epinephrine makes a stimulatory G protein complex to activate adenylyl cyclase- production of cAMP
- But an inhibitory protein such as adenosine makes an inhibitory G protein complex which deactivates adenylyl cyclase- no production of cAMP
What is meant by the intergation of signals?
When 2 signals have opposite effects on metabolic characterist
-so the overall effect and strength is based on the concentration of each one (which one cancels out)
What is the specificity of a signal molecule?
That a signal molecule fits to binding site on complementary receptor - other signals don’t fit
