L18: Cell Signalling Flashcards
What is the general principle of signal transduction in cells?
Signals, often occurring outside the cell, are transduced and interpreted inside the cell, allowing the cell to respond appropriately.
Name four main types of cell signalling based on distance.
- Endocrine: Long-distance (e.g., hormones like insulin).
- Paracrine: Signals to nearby cells.
- Neuronal: Via neurotransmitters.
- Contact-dependent: Direct cell-to-cell contact.
What role do receptors play in cell signalling?
Receptors detect specific signals and initiate signal transduction, converting the extracellular signal into an intracellular response.
How do the same signals elicit different responses in various cells?
Responses depend on the receptor type and intracellular machinery unique to each cell.
What happens to a cell if it receives no survival signals?
It undergoes apoptosis (programmed cell death).
Differentiate between fast and slow cellular responses to signals.
• Fast responses: Modify existing proteins (e.g., phosphorylation).
• Slow responses: Involve transcription and translation, requiring new proteins to be made.
What are protein kinases, and what do they do?
Protein kinases are enzymes that phosphorylate proteins on serine, threonine, or tyrosine residues, altering their activity or creating docking sites.
What is the function of GTPases in cell signalling?
GTPases act as molecular switches, cycling between an active (GTP-bound) and inactive (GDP-bound) state to regulate signalling pathways.
Describe G-protein-coupled receptors (GPCRs).
GPCRs are cell surface receptors that span the membrane 7 times and, upon activation by a ligand, signal through trimeric G-proteins to initiate cellular responses.
What are second messengers? Provide examples.
Second messengers amplify and distribute signals within the cell. Examples include cyclic AMP (cAMP) and calcium ions.
Outline the role of phospholipase C (PLC) in signal transduction.
PLC cleaves PIP2 into DAG (diacylglycerol) and IP3 (inositol triphosphate), which respectively activate protein kinase C and release intracellular calcium.
What is the significance of the Ras protein in cell signalling?
Ras is a GTPase that activates downstream kinases in the MAPK pathway, driving processes like cell proliferation.
What is receptor tyrosine kinase (RTK) signalling?
RTKs, activated by dimerisation and autophosphorylation upon ligand binding, recruit adaptor proteins to propagate intracellular signals.
What are examples of clinical applications derived from signalling pathway knowledge?
• Herceptin (trastuzumab): Targets HER2-positive breast cancer.
• Vemurafenib: Inhibits mutant BRAF in metastatic melanoma.
What are the three main types of cell surface receptors?
- Ion channel-coupled receptors.
- G-protein-coupled receptors (GPCRs).
- Enzyme-coupled receptors (e.g., receptor tyrosine kinases).
How does cortisol mediate its effects?
Cortisol, a steroid hormone, diffuses across the plasma membrane, binds to an intracellular receptor, and together they regulate gene transcription in the nucleus.
What is the role of nitric oxide (NO) in cell signalling?
NO diffuses across membranes, affecting smooth muscle cells to regulate vascular tone and blood pressure.
What is the function of cyclic AMP (cAMP) in signalling?
cAMP, generated from ATP by adenylyl cyclase, acts as a second messenger to activate protein kinase A (PKA) and regulate various cellular processes.
How is cAMP signalling terminated?
cAMP is degraded to AMP by cyclic AMP phosphodiesterase, switching off the signal.
Explain the concept of a kinase cascade using the MAPK pathway.
In the MAPK pathway:
• Ras activates Raf.
• Raf phosphorylates MEK.
• MEK phosphorylates ERK (MAPK).
• ERK activates transcription factors to promote cell cycle progression.
What are the two main outcomes of calcium signalling?
- Activation of calcium-responsive proteins like calmodulin.
- Regulation of processes like muscle contraction, secretion, and enzyme activity.
What happens during the activation of receptor tyrosine kinases (RTKs)?
Ligand binding causes dimerization of RTKs, activating their kinase domains, leading to autophosphorylation and recruitment of adaptor proteins.
What is the role of Grb2 in RTK signalling?
Grb2 is an adaptor protein that binds phosphorylated tyrosine’s on RTKs and recruits SOS, a Ras-activating protein.
Why is Ras commonly mutated in cancer?
Mutations in Ras often prevent its GTPase activity, locking it in an active state, leading to uncontrolled cell proliferation.
What are the products of phospholipase C (PLC) activity, and what do they do?
• DAG (diacylglycerol): Activates protein kinase C (PKC).
• IP3 (inositol triphosphate): Triggers calcium release from intracellular stores.
What is the function of protein kinase C (PKC)?
PKC phosphorylates various target proteins, regulating processes such as metabolism, gene expression, and cell motility.
What is the role of calmodulin in calcium signalling?
Calmodulin binds calcium, undergoes a conformational change, and activates target proteins or enzymes involved in signalling.
How do cells integrate multiple signalling pathways?
Cells use signalling proteins modified by multiple post-translational modifications (e.g., phosphorylation) to integrate inputs from different pathways into a coordinated response.
How does HER2 amplification affect breast cancer prognosis?
HER2 amplification leads to increased proliferation of breast cancer cells and correlates with a poor prognosis, treatable with Herceptin (trastuzumab).
What is vemurafenib, and what mutation does it target?
Vemurafenib is a drug targeting mutant BRAF in metastatic melanoma, inhibiting aberrant MAPK pathway activation.
