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