chapter 13: signal-transduction pathwaysdmohnen/bcmb3100/carlson... · receptor proteins...
TRANSCRIPT
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CHAPTER 13: Signal-Transduction Pathways(Problems: 1-5,7,13,15-18,21,25,29)
1. Primary messenger.• Signal, first messenger, ligand.
2. Reception of primary messenger.• Protein receptor of primary messenger.
3. Relay of information.• Transmembrane protein, transducer.
4. Activation of effectors.• Transducer, effector enzyme,
second messenger, effectors.5. Termination of signal.
• Phosphatases
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13.2. Receptor Proteins
Transmembrane proteinsSeven transmembrane helices(7TM proteins)
Ligand binding on outside leads to conformational change (new activity) on inside of cell.
Ligand Binding
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ligand
7TM receptor
Transducer(G-protein)
Effectorenzyme
Secondmessenger
Effector
Gs
Ligand Binding → Activation of G-Proteins →Activation of Effector Proteins
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Activation of Effector Proteins →Phosphorylation of Proteins
Protein kinase A
Protein kinase A phosphorylates Ser and Thr residues in numerous proteins resulting in activation or inhibition of their functions.
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Control of Activation
XGTP
XChlorera (Vibrio cholorae)Choleragen → stabilizes Gs
↓Open Cl‐ channel
↓Inhibits Na+‐H+ exchange
↓NaCl loss
G-cycle
Whooping Cough (Bordertella pertussis)Toxin → prevents Gi
↓Closes K+ channel
↓Opens Ca2+ channel
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Reversible Ligand/Receptor Binding
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Other Second Messengers
Ligand/Receptor binding leads to G‐protein activation
2nd messenger 2nd messenger
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Phosphorylation of Ser and thron many proteins
The Phosphoinositide Cascade
Ligand + Receptor
Active G‐Protein
Activates C
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13.3. Tyrosine Kinases
Epidermal Growth Factor Signaling
Adaptor proteinsPi
Tumors
X
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13.4. Insulin Signaling
Akt is a mobile protein kinase
Insulin-receptor substrates
Phosphorylate enzymes in glycogen synthesis and glucose transport (GLUT4)
Signaling terminated by protein phosphatases
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13.4. Calcium Ion is a Cytoplasmic Messenger
CaM-Ca2+ CaM-Kinase+
Inactive
CaM-Ca2+
CaM-KinaseActive
Phosphorylation of proteins resulting in regulation of fuel metabolism, ion permeability, neurotransmitters