CHAPTER 13: Signal-Transduction Pathwaysdmohnen/bcmb3100/CARLSON... · Receptor Proteins Transmembrane proteins Seven transmembrane helices (7TM proteins) Ligand binding on outside
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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
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
ligand
7TM receptor
Transducer(G-protein)
Effectorenzyme
Secondmessenger
Effector
Gs
Ligand Binding → Activation of G-Proteins →Activation of Effector Proteins
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.
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
Reversible Ligand/Receptor Binding
Other Second Messengers
Ligand/Receptor binding leads to G‐protein activation
2nd messenger 2nd messenger
Phosphorylation of Ser and thron many proteins
The Phosphoinositide Cascade
Ligand + Receptor
Active G‐Protein
Activates C
13.3. Tyrosine Kinases
Epidermal Growth Factor Signaling
Adaptor proteinsPi
Tumors
X
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
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
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