SIGNAL TRANSDUCTION

INTRODUCTION

• Signal transduction occurs when an extra cellular signaling molecule activates a

cell surface receptor.

• Inturn receptor alters intracellular molecules creating a response.

• 2 major steps involved in signal transduction are

* A signaling molecule activates a specific receptor protein on the cell

membrane .

* A second messenger transmits the signal into the cell, eliciting a

physiological response.

• In either step the signal can be amplified. Thus a single molecule can cause many

response.

MECHANISM OF SIGNAL TRANSDUCTION

• Signal transduction through cell membranes depends on membrane

proteins and phospholipids.

• The process used for transduction vary for different ligands.

• Each will follow a general series of events.

• At least four types of protein are used:

* Receptor (binding site protein)* G protein* Adenylate cyclase* Protein kinases

Hormones (or neurotransmitters) bind to the specific receptors.

G

extracellular fluid

adenylate

cyclase

cytoplasm

Ligand-receptor binding stimulates the receptor to interact with a G protein inthe inner membrane.

“G” because the protein will bind guanine nucleotides (GDP, GTP).* G proteins are heterotrimers* Associate with the membrane receptor* Has 3 sub units: Alfa, Beta and Gamma. In inactivated form

GDP is associated with the Alfa sub unit.* Ligand binding causes GTP exchange and Dissociation of the

Alfa subunit.

G

GTP GDP

extracellular fluid

adenylate

cyclase

cytoplasm

Activated G protein passes signal to an enzyme (for Exp., adenylate cyclase) and

stimulates (or inhibits it).

G

Adenylate

cyclase

Extracellular fluid

Intracellular fluid

Adenylate cyclase catalyzes the formation of cyclic adenosine monophosphate (cAMP)

from ATP.

After the production of cAMP is stimulated, these cAMP will bind to proteins called

protein kinases A , causing the removal of regulatory subunits of the protein and

activation of the catalytic subunits. These activated protein kinases inturn activates

phosphorylase kinase .. They will cause the phosphorylation of intracellular proteins.

After phosphorylation, some enzymes may become more active, others may become

less active.

The cellular activity is thus modifies.

G

ATP

cAMP

extracellular fluid

adenylate

cyclase

cytoplasm

Three second messenger systems have been identified, based on the membrane proteins

involved:

1). Adenylate cyclase (cAMP) system;

2). Phospholipase C (IP3) system;

3). Tyrosine kinase system

Phospholipase C – IP3 – Ca2+ Second Messenger System

• Binding of epinephrine to the -receptors stimulates a totally different intracellular cascade.

• A membrane enzyme, phospholipase C is activated via G-protein (, complex).

• Two secondary messengers, IP3 and DAG are generated.

• The binding of IP3 and its receptor causes the opening of Ca++ channel on the

endoplasmic reticulum membrane.

• Ca2+ will be released from ER into the cytoplasm down…they will act as the

secondary messengers.

THANK YOU