Lecture 9 -signalling Flashcards
(15 cards)
Step 1: Signal Origination — Types of Extracellular Mediators
Hormones
Endocrine action: blood-borne, long-distance.
Example: Adrenaline → short-term metabolic effects (e.g., glucose mobilization).
Growth Factors
Paracrine/autocrine: act on nearby/self cells.
Example: Platelet-derived growth factor → triggers cell proliferation during wound healing.
Steroid Hormones
Intracellular action: pass through membranes to bind cytosolic or nuclear receptors.
Example: Estrogen → long-term gene expression changes in development.
Step 2: Signal Detection: three major receptor types:
Ion Channel Receptors (Ligand-Gated Ion Channels)
G Protein-Coupled Receptors (GPCRs)
Enzyme-Linked Receptors
second step: Signal binds to its matching receptor, initiating transduction.
Step 2: Signal Detection: Ion Channel Receptors (Ligand-Gated Ion Channels)
Open upon ligand binding → allow ions to flow → electrical and chemical changes.
Example: Acetylcholine opens Na⁺ channels → muscle contraction.
Step 2: Signal Detection: G Protein-Coupled Receptors (GPCRs)
7-transmembrane domain proteins.
Activate intracellular G-proteins → trigger second messenger production.
Example: Adrenaline activates β-adrenergic receptors → cAMP pathway.
Step 2: Signal Detection: Enzyme-Linked Receptors
Either have intrinsic enzymatic activity (e.g., receptor tyrosine kinases) or recruit enzymes.
Usually linked to long-term effects like proliferation.
Example: Insulin receptor activates downstream kinases → promotes glucose uptake.
Step 3: Signal Transduction — Second Messengers
Once a receptor is activated, it triggers the production/release of second messengers.
Criteria for Second Messengers:
Small molecules (e.g., ions, metabolites).
Rapidly produced and degraded.
Controlled by extracellular signals.
Trigger specific changes inside the cell (amplification of signal).
Major Second Messengers: cAMP
Activates PKA → lipid breakdown, glycogen synthesis inhibition.
Major Second Messengers: cGMP
Activates PKG → regulates smooth muscle tone, phototransduction.
Major Second Messengers: DAG
Activates PKC → modulates transcription and metabolism.
Major Second Messengers: IP3
Opens Ca²⁺ channels in ER → triggers Ca²⁺ signalling cascades.
Ca²⁺ ions
Bind to calmodulin, activate kinases → regulate movement, secretion, gene expression.
Step 4: Amplification through Kinase Cascades
Once second messengers are active, kinase cascades are used to amplify and diversify the response:
Kinases: enzymes that add phosphate groups to proteins (on Ser, Thr, or Tyr residues).
Phosphorylation can:
Activate enzymes.
Modify protein-protein interactions.
Alter protein stability.
Change gene expression.
Example of Amplification (Epinephrine → cAMP Pathway):
- One epinephrine molecule binds to one GPCR (β-adrenergic receptor).
- The GPCR activates many G-proteins (each receptor can activate multiple G-proteins while ligand-bound).
- Each active G-protein (specifically Gαs) then activates one adenylyl cyclase.
- Each adenylyl cyclase enzyme produces hundreds to thousands of cAMP molecules from ATP.
- Each cAMP molecule then activates one PKA (protein kinase A) (PKA is a tetramer and requires binding of 4 cAMPs to fully activate, but simplified: each cAMP helps).
- Each activated PKA phosphorylates many target proteins/enzymes (amplifying the signal even further).
- Some phosphorylated enzymes (like phosphorylase kinase) can themselves activate other enzymes (like glycogen phosphorylase) → causing huge metabolic changes.
Step 5: Cellular Response
Signal transduction leads to actual changes in the cell, such as:
Modification of metabolism
(e.g., breaking down glycogen in muscle during fight-or-flight).
Changes in movement
(e.g., white blood cells moving toward infection).
Altered gene expression
(e.g., growth factors leading to new protein synthesis).
Control of cell proliferation or differentiation
(e.g., stem cells committing to specific fates during development).
