Signal Transduction Pathways

• An introduction to Information metabolism

• Chapter 15 Stryer Biochemistry

Signal Transduction

• 1) Membrane receptors transfer information

• 2) Second messengers relay information from the receptor ligand complex.

• 3) Protein phosphorylation is a common means of information transfer

Second messengers

Second messengers

Second messengers

Second messengers

Protein Phosphorylation

7TM helix receptors

• The 7TM helix receptors change conformation upon binding of ligand and activate a G-Protein

• Rhodopsin

• Β-adrenergenic receptor

Activated G-Protein transmits signal by binding to other proteins

G-Protein binding to adenylate cyclase increases the catalytic efficiency of the adenylate cyclase and increases the synthesis of cAMP inside the cell

G-Proteins spontaneously reset themselves

Resetting the G-Protein

Receptor resetting

cAMP stimulates the phosphorylation of many target

proteins by activating PKA

• 1) Glycogen metabolism

• 2) Expression of specific genes (CREB)

• 3) Synaptic transmission– Serotonin binds to a 7TM helix receptor– cAMP activates PKA– PKA facilitates the closing of K channels by

phosphorylation

Hydrolysis of Phosphatidyl inositol Bisphosphate

What are the biocehmical effects of IP3?

• IP3 causes the rapid release of Ca from intracellular stores (ER, SR)

• Causes smooth muscle contration

• Glycogen breakdown

• Vesicle release

Diacylglycerol activates PKC

Ca Ion is a ubiquitous cytosolic messenger

Ca activates the regulatory protein Calmodulin

Regulation of Calmodulin of Calmodulin kinase

Receptor dimerisation

JAK phosphorylates STAT5

Some receptors contain a tyrosine kinase domain within their covalent structures

Defects in signaling pathways can lead to cancer and other diseases