BIO270H1 Lecture Notes - Lecture 5: Phosphatidylinositol, Cgmp-Dependent Protein Kinase, Adenylyl Cyclase

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Lecture 5
Signal Transduction Pathways
o Convert the change in receptor shape to an intracellular response
o 4 Components
Receiver
Ligand-binding region of receptor
Transducer
Conformation change of the receptor which activates
Amplifier
Signal transduction cascade
Increases number of molecules affected
Responder
Molecular functions that change in response to signal
Transduction Pathway
o Ligand binds to receptor and continues to activate
o Amplification of molecules
Types of Receptors
o Intracellular
Hydrophobic ligand
Used to cross membrane
Most for genomic effects
o Ligand-gated ion channels
Changes in membrane potential
Rapid response
o Receptor enzymes
Changes in membrane potential
Rapid
o G-Protein coupled
Activation of G bound proteins
Rapid changes
Intracellular Receptors
o Regulate transcription in target cells
o Hydrophobic ligands the cell membrane
o Inside the cell the ligand binds to ligand binding domain of
intracellular receptors
o Ligand binding changes conformation
o Receptor-ligand complex translocate to the nucleus
o DNA binding domain binds to DNA
o Together it helps regulate the transcription of mRNA
Ligand gated ion channels
o Ligand binds to transmembrane receptors
o Receptors open
o Travels down the electrochemical gradient
o Direct and rapid
Receptor enzymes
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o Ligand binds to transmembrane receptors
o Receptors dimerize and autophosphorylate
o Protein kinases signals to Ras protein
o Ras switches between active and inactive forms
G-protein coupled receptors
o Ligand-receptor interacts with intracellular G-protein
o Bond guanine nucleotides
o Heterotrimetric
o Ligand binds to a G-protein coupled receptors
o Causes alpha subunit to release GDP and bind GTP
o Activated alpha or beta-gamma subunits more through membrane to
amplify enzyme
o Activated amplifier enzyme converts an inactive second messenger
into its active form
o Subunits of the G-Protein
Activate ion channels
Activates amplifier enzyme: 2nd messengers
Second Mesengers
o A short lived intracellular messenger that acts as an intermediate in
signal transduction pathway
o Ca2+, cGMP, cAMP and phosphatidyl inositol
Second Messenger
Synthesized by the
enzyme
Action
Effects
Ca2+
None
Binds to calmoduli
Alters enzymes
activity
cGMP
Guanylate Cyclate
Activates protein
kinases (usually
protein kinase G)
Phosphorylate
proteins. Open and
closes ion channels
cAMP
Adenylate Cyclase
Activates protein
kinases (usually
protein kinase A)
Phosphorlytes
proteins. Open and
closes ion channels
Phosphatidyl
inositol
Phospholipase C
Activates protein
kinase C.
Stimulates Ca2+
release from
intracellular stores
Allows enzyme
activity.
Phosphorylate
proteins.
Lignad binds
Inositol-Phospholipid Signaling
o Ligand binds to a G protein, causing a conformational change
o Alpha subunit of G protein is released and binds GTP and moves
through the membrane
o Activated alpha subunit activates phospholipase C, which cleaves PIP2
into IP3 and DAG
o DAG is cleaved and forms arachidonic acid, the substrate for synthesis
of chemical messengers called eicosanoids
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Document Summary

Signal transduction pathways: convert the change in receptor shape to an intracellular response, 4 components. Conformation change of the receptor which activates. Molecular functions that change in response to signal. Transduction pathway: ligand binds to receptor and continues to activate, amplification of molecules. Most for genomic effects: ligand-gated ion channels. Ligand gated ion channels: ligand binds to transmembrane receptors, receptors open, travels down the electrochemical gradient, direct and rapid. Receptor enzymes: ligand binds to transmembrane receptors, receptors dimerize and autophosphorylate, protein kinases signals to ras protein, ras switches between active and inactive forms. Second mesengers: a short lived intracellular messenger that acts as an intermediate in signal transduction pathway, ca2+, cgmp, camp and phosphatidyl inositol. Guanylate cyclate activates protein kinases (usually protein kinase g) Interaction among transduction pathways: cells have receptor for different ligands, response of the cell depends on complex interactions, ex. Ca2+-cam interacts with adenylate cyclase and camp pde: pka can phosphorylate ca2+-channels.

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