Chapter 14: Signal Transduction

General signal transduction steps

Primary messenger: a ligand that binds to the specific receptor on or within a cell’s surface

• Hormones

• Physical changes

• A meal

• Temperature

• Viral or Bacterial infection

Reception of primary messenger:

• 7TM proteins

Generation of second messenger:

• cAMP, cGMP, Ca²⁺, inositol, IP3

Activation of effector:

• Phosphorylation of proteins

• Activation of Enzymes

• Activation or repression of gene expression

Termination of the signal

Properties of primary messengers

1. Epinephrine Signaling

   1. b-AR, a 7-TM protein

2. Insulin Signaling

   1. A meal

   2. Production of insulin

3. EGF signaling

   1. Epidermal growth factor

Structural features of membrane receptors for epinephrine, insulin and EGF.

Epinephrine (b-AR)

• G protein-coupled receptor (GPRC)

• Structure: contains seven transmembrane helices

• Activation:

  1. b-AR binds to epinephrine

  2. Activates Gs proteins

  3. Starts cAMP production

  4. Leads to the activation of PKA

Insulin (Tyrosine Kinase)

• 2 alpha and 2 beta subunits

• Activation: Insulin biding inducing autophosphorylation

EGF (Tyrosine Kinase)

• Dimerization upon ligand binding

• Dimerization leads to autophosphorylation and downstream signaling

• Activation:

  1. Promotes receptor dimerization and autophosphorylation

  2. Initiates the Ras-MAPK signaling cascade

  3. Involves proteins like Grb2 and SOS

What is the difference between G-protein and Ras protein?

Structure:

Heterotrimeric vs monomeric

Signaling:

GPCRs vs RTK pathways

Activation Mechanisms:

Different regulatory proteins and processes