Cell Signalling Flashcards
What are the different inputs and outputs of cell signalling
What is the w general cell signalling pathway
What are the different type of cell signalling
What are the different types of signal molecules
How are most signal molecules recieved by the target cell
How are hydrophobic signals received by a target cell
How can animal cells respond to multiple signal outputs
With the example of acetylcholine, explain how the same signal molecules recurved can elicit different responses
What can off to on transitions of signal nodes be done
What are the different effects of PTMs
What is meant by the writer, reader, eraser system of PTMs
How many human protein kinases are there
How is kinase activity regulated
In its inactive, unphosphorylated form, critical residues in the activation loop are in the wrong position to bind ATP and its protein substrates. When a critical threonine residue in the activation loop is phosphorylated by PKA or by another kinase, the conformation of the loop changes, creating the binding site for ATP and its substrates, thus activating catalytic activity.
What do many anti cancer drugs do
What are molecular switches
Why at the two features of signal transduction pathways
How can signalling specificity be increased
How can multivalency and membrane association increase signalling *
Multivalent interactions are collectively stronger than individual monovalent interactions. For example, proteins with multiple binding sites can form stable complexes even if individual interactions are weak.
• This ensures stable and prolonged signaling even at low concentrations of signaling molecules.
Many signaling events occur at cellular membranes, where receptors, lipids, and signaling proteins are concentrated. Membrane association involves the recruitment or localization of signaling molecules to the lipid bilayer.
What is DNA-induced liquid phase condensation of cGAS
What determines the speed of a response
What is a transient response
What is a long lasting response
What are the signalling networks notation
How does positive feedback loops work *
Signals are amplified in positive feedback loops through a process of self-reinforcement, where an initial signal stimulates a response that feeds back into the system to further enhance the signal. This leads to exponential or sustained increases in the signal strength
By:
Increase activation of components involved in signalling pathways
Amplify ion influxes
Induce clustering of receptors
Increase production of secondary messengers
How does negative feedback loops work *
Negative feedback loops are mechanisms where the output of a process inhibits or reduces its own activity.
The effector’s action decreases the initial stimulus, bringing the system back toward its set point.
• As the system stabilizes, the negative feedback signal weakens, reducing the effector activity.
How does positive feedback result in switch like responses*
Positive feedback can create switch-like responses because it reinforces itself, driving the system toward one of two distinct, stable states (e.g., “on” or “off”)
The system requires a minimum (threshold) input to activate the feedback loop. This prevents noise or weak signals from triggering the response.
Once the feedback loop is triggered, the system rapidly moves to the “on” state, and the response becomes essentially irreversible until other mechanisms (e.g., negative feedback) intervene to reset the system.
How does negative feedback reduce the strength or duration of a signal
How can negative feedback with a delay result in oscillations *
Negative feedback with a delay can result in oscillations because the delayed response causes the system to “overshoot” its equilibrium point, creating periodic fluctuations around the set point
Explain AND, NOR, OR and XOR logic gates
How can Combining a feedforward loop with an AND gate create a sustained input detector in cell signalling *
Eg a signal A activates a response, but it does so in two ways:
1. Fast Path: A directly activates the response quickly.
2. Slow Path: A also activates a helper molecule (A) that takes longer to build up before it helps activate the response.
Now add an AND gate: The response only happens if both the fast path and the slow path are active at the same time.
How It Detects Sustained Input:
• If the signal A is short-lived, the fast path turns on briefly, but the slow path doesn’t have enough time to catch up, so the response doesn’t happen.
• If the signal A is sustained, both paths overlap in time, and the AND gate activates the response.
This setup filters out “noisy” or temporary signals and responds only to signals that last long enough.
Give examples of signals that can activate GPCRs
What is meant by the terms :
Full agonist
Partial agonist
Neutral antagonist
Inverse agonist *
A full agonist is a molecule that binds to a receptor and produces the maximum possible response (100% activation)
A partial agonist binds to the receptor and produces a response, but it is weaker than the maximum response of a full agonist, even at full receptor occupancy.
neutral antagonist binds to the receptor but does not activate it or produce any response. Instead, it blocks other molecules (like agonists) from binding and activating the receptor.
An inverse agonist binds to the receptor and reduces its activity below its baseline level (even if no agonist is present). This occurs in receptors that have constitutive activity (activity in the absence of a ligand). - It stabilizes the inactive state of the receptor, effectively turning it off.
How does the β2-adrenergic receptor work*
What are the different GPCR families
How are GPCRs generally activated
What are the different models of GPCR activation
Explain the extended tertiary complex model of GPCR activation*
Receptor can naturally flip to active state even without anything bound
Different ligands can bind receptor and change how much the receptor spends in its active state (ie full agonist partial etc )
When a G-protein binds to the receptor, it helps stabilize the receptor’s active state (R^*), making it more likely to send signals.
• Ligand binding and G-protein binding work together to amplify the signal.
What is the role of adenylyl cyclase
How is PKA activated
What is the role of somatostatin
How is the fight or flight response mediated by PKA
What is the role of Phospholipase C-β *
Phospholipase C-beta (PLC-β) is an enzyme that functions as a key player in cellular signal transduction. It is activated by G protein-coupled receptors (GPCRs) and plays a crucial role in generating second messengers involved in various physiological processes. Here’s an overview of how it works:
- Activation of GPCRs:
• A signaling molecule (ligand), such as a hormone or neurotransmitter, binds to a GPCR on the cell membrane.
• This causes a conformational change in the GPCR, which allows it to interact with and activate a heterotrimeric G protein (composed of α, β, and γ subunits). - G protein activation:
• Upon interaction with the activated GPCR, the Gα subunit exchanges GDP for GTP and dissociates from the βγ subunits.
• Depending on the G protein subtype, PLC-β is activated by either the Gαq subunit or the Gβγ complex. - Activation of PLC-β:
• Once activated, PLC-β catalyzes the hydrolysis of a specific membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP₂), into two important second messengers:
• Inositol 1,4,5-trisphosphate (IP₃): A soluble molecule that diffuses through the cytoplasm.
• Diacylglycerol (DAG): A lipid molecule that remains in the plasma membrane. - Downstream signaling:
• IP₃ binds to its receptor on the endoplasmic reticulum (ER), causing the release of stored calcium ions (Ca²⁺) into the cytoplasm. This increase in cytosolic Ca²⁺ can activate various calcium-dependent signaling pathways.
• DAG works synergistically with Ca²⁺ to activate protein kinase C (PKC), a family of serine/threonine kinases that regulate various cellular processes such as gene expression, metabolism, and cell proliferation. - Signal termination:
• The signal is terminated by hydrolysis of GTP to GDP on the Gαq subunit, leading to its reassociation with the Gβγ subunits and inactivation of PLC-β.
• Additionally, enzymes like phosphatases and kinases regulate the levels of IP₃, DAG, and calcium to restore the resting state.
What is the role of calmodulin
Calmodulin activates or inhibits many enzymes in response to calcium signals. Key examples include:
• Calmodulin-dependent protein kinases (CaMKs): These kinases phosphorylate target proteins, regulating cellular processes like gene transcription, metabolism, and synaptic plasticity.
• Adenylyl cyclases and phosphodiesterases: Calmodulin modulates cyclic AMP (cAMP) and cyclic GMP (cGMP) levels by regulating these enzymes.
- Control of Ion Channels and Pumps:
• Calmodulin regulates the activity of various calcium, sodium, and potassium ion channels, as well as pumps such as:
• Plasma membrane Ca²⁺-ATPases (PMCAs): Calmodulin enhances calcium extrusion to restore resting calcium levels.
• Voltage-gated calcium channels: Calmodulin modulates their opening and closing. - Role in Muscle Contraction:
• In smooth muscle, calmodulin activates myosin light-chain kinase (MLCK), which phosphorylates myosin, leading to contraction. - Regulation of Cellular Motility and Cytoskeleton:
• Calmodulin interacts with cytoskeletal proteins, influencing processes such as cell division, migration, and intracellular transport.
How does the HES27 negative feedback loop work
What is the anatomy of the olfactory system
How many odorant receptor (OR) genes do humans have
What is meant by the combinatorial coding of olfactory info
How does odorant receptor signalling work
What is the anatomy of the retina
How do rod photo sensor works (brief description )
What is rhodopsin
Explain in more detail what happens in rod cells in the dark
Explain in more detail what happens in rod cells in light
What happens if we inhibit the cGMP phosphodiesterase
More inhibitor of cGMP phosphodiesterase = less response to light
Describe the signal amplification pathway in rod cells
How is signalling terminated in rod cells
How does signal transduction by beta arrestins work
How are GPCRs internalised
How do receptor tyrosine kinases (RTKs) generally work
What are RTKs
How many RTKs does the human genome encode
How are RTKs expressed in cancer
How is RTK activation and signalling studied
How does western blotting work
How are RTKs activated
How is epidermal growth factor (EGF) receptor dimerised
What are the exceptions to the ligand induced RTK dimerisation method of activation
How is insulin receptor kinase activated
How is the activation loop of kinases phosphorylated
How is the EGF RTK activated
What can the phosphorylated tyrosine residues in RTKs be used for
What domains recognise phosphotyrosines
What different domains can be present in signalling proteins
What are Src tyrosine kinases
How do a variety of cellular effectors and adaptors bind to phosphotyrosines using SH2 and PTB
domains*
The N-terminal side of the SH2 domain contains a hydrophobic pocket that accommodates the pTyr residue, allowing for tight binding.
The SH2 domain recognizes both the phosphotyrosine itself and the surrounding sequence. The specificity of binding is determined by the amino acid residues flanking the pTyr (especially on the C-terminal side).
The PTB domain typically binds to a consensus sequence of pY-X-X-X- (again, “Y” is phosphorylated tyrosine, and “X” is other amino acids).
PTB domains also engage in a direct interaction with the pTyr residue, but the structural context of the phosphotyrosine recognition can vary slightly, and the sequence surrounding it can often be more variable than with SH2 domains.
Outline the Ras-MAP kinase pathway
What is Ras
How is Ras anchored to the membrane
Step one of Ras-MAP pathway
Step two of Ras-MAP pathway
What is the problem with the the Ras-MAP pathway
Scaffold proteins physically organise MAP kinase modules
What is the role ERK *
Is MAP kinase (MAPK)
ERK translocates to nucleus and phosphorylates TF such as AP1 (AP1 formed from c- fos and c-jun complex)
AP1 complex binds AP1 binding suites on c fos gene
What does sustained MAPK activation result in
How does ERK participate in multiple negative feedback loops
What is the role of PLC-γ
What is the role of Phosphoinositide 3-kinase (PI3K)
What is PIP3 recognised by
Describe the PI3K/Akt pathway
Why does PTEN do
How is RTK Signalling terminated
What is the role of Cbl
How does transient vs sustained response arise in PC12 cells
