cell bio lecture 14

What is a signalsome? 🧩

A signalsome is the unique combination of receptors, G proteins, kinases, and target proteins expressed in a cell that determines how it responds to signals 🎯

Why can the same hormone produce different effects in different tissues? 🔄

Different tissues express different receptors and downstream proteins, so the same signal activates different pathways and outcomes 🧠

What hormones mediate the fight-or-flight response? ⚡

Adrenaline and noradrenaline mediate fight-or-flight by increasing heart rate, energy release, and alertness 🚨

What is the difference between adrenaline and noradrenaline? 🧠

Adrenaline acts systemically via the blood, while noradrenaline acts locally at nerve endings 📍

Why are adrenergic receptors divided into α and β types? 🧲

Different receptor subtypes explain how the same hormone can cause different physiological effects in different tissues 🎛️

What type of receptor is the β-adrenergic receptor? 🔗

The β-adrenergic receptor is a G-protein-coupled receptor (GPCR) that signals through Gαs and cAMP 📡

Describe what happens in β-adrenergic GPCR signal transduction via the cAMP–PKA pathway.🔄

Adrenaline binds β-adrenergic GPCR → GPCR activates Gαs (GDP→GTP) → Gαs activates adenylyl cyclase → ATP converted to cAMP → cAMP binds PKA regulatory subunits → catalytic subunits released → PKA phosphorylates target proteins ⚡

What is cAMP and why is it important? 🧪

cAMP is a second messenger that carries signals from the membrane to intracellular targets like PKA, allowing signal amplification 📈

How does adenylyl cyclase contribute to signalling? 🔬

Adenylyl cyclase converts ATP into cAMP after activation by Gαs, initiating downstream signalling 🧠

How is Protein Kinase A (PKA) activated? 🔓

PKA is inactive as a holoenzyme (2 regulatory + 2 catalytic subunits); cAMP binds regulatory subunits, releasing active catalytic subunits ✂️

Why is phosphorylation considered signal amplification? 📈

One activated kinase can phosphorylate many targets, rapidly amplifying a single hormonal signal 🚀

Describe how adrenaline causes glycogen breakdown in liver and muscle 🍬 (pathway)

Adrenaline → β-adrenergic receptor → cAMP → PKA → phosphorylase kinase → glycogen phosphorylase → glycogen broken down to release glucose ⚡

How does phosphorylation activate glycogen phosphorylase? 🔧

Phosphorylation at Ser14 causes a conformational change that activates the enzyme, showing long-range structural control 🧠

How does PKA coordinate glycogen breakdown and synthesis? ⚖️

PKA activates glycogen breakdown while inhibiting glycogen synthesis, ensuring energy is released efficiently 🔥

What is the role of β-adrenergic signalling in adipose tissue? 🧈

PKA phosphorylates hormone-sensitive lipase and perilipin, allowing lipolysis and release of free fatty acids ⚡

What is the effect of β-adrenergic signalling in cardiac muscle? ❤️

PKA phosphorylates calcium-handling proteins, increasing calcium flux, contraction strength, and relaxation speed 💓

Why are AKAPs important in signalling? 🧩

AKAPs anchor PKA to specific locations, ensuring precise and localized phosphorylation 🧭

What determines tissue-specific outputs of cAMP signalling? 🧬

Different tissues express different PKA substrates, so the same pathway produces different physiological effects 🎯

How is GPCR signalling switched off? 🚦

Gα hydrolyses GTP to GDP,

GPCRs are phosphorylated by GRKs,

β-arrestin blocks G-protein binding,

receptors are internalised,

cAMP is degraded by PDEs, and phosphatases remove phosphates 🛑

What is receptor desensitisation? 🔒

Desensitisation occurs when GPCRs are phosphorylated and bound by β-arrestin, reducing further signalling despite ligand presence ⛔

Why is tight regulation of GPCR signalling essential? ⚠️

Tight regulation prevents overstimulation, maintains homeostasis, and protects cells from damage 🧠

What is the main takeaway of β-adrenergic signalling? 🎯

A shared GPCR–cAMP–PKA pathway can produce diverse, tissue-specific outcomes due to different signalsomes 🧩