4.2 Signal Transduction

4 Steps of Signal Transduction

1. Signaling

   • Cell A creates a ligand

2. Reception

   • Ligand binds to receptor on Cell B

3. Transduction

   • Pathways connect Reception to Response

4. Response

   • Cell B undergoes desired change

Signal Transduction

transmission of a molecular signal from outside to inside the cell to induce a biological response

3 Methods of Reception

1. Intracellular receptors

2. Ligand gated ion channels

3. Cell surface receptors

3 Responses

1. Cellular metabolism

   • Target: cytoplasmic enzyme

2. Cell shape/movement

   • Target: cytoskeletal elements

3. Gene expression

   • Target: nuclear gene

Gene expression response target

nuclear gene

Cellular Metabolism response target

cytoplasmic enzyme

Cell shape/movement response target

cytoskeletal elements

Pathway

a series of molecular interactions in a biological system

ex. glycolysis

Cascade

a signaling pathway

Upstream - toward the signal

Downstream - toward the response

Common Patterns in Signal Transduction

1. Secondary Messengers

2. Phosphorylation

3. Signal Amplification

Secondary Messengers

Small, non-protein molecules that pass along the signal

• original ligand is the primary messenger

• ex.

  • Na+

  • Cl-

  • Ca+

  • cAMP

    • created by Adenylyl Cyclase

cAMP

created by adenylyl cyclase

secondary messenger

Phosphorylation

Many proteins are turned “On/Off” by adding a phosphate and turned “Off/On” by removing a phosphate

• phosphate typically linked to one of the three amino acids that have hydroxyl (-OH) groups in their side chains

  • tyrosine, threonine, serine

Kinase - enzyme that adds a phosphate

Phosphatase - enzyme that removes a phosphate

3 Amino Acids with Hydroxyl (can be phosphorylated)

tyrosine, threonine, serine

Signal Amplification

The signal from one ligand-receptor complex can be amplified as the signal moves downstream

Signals that amplify more are sensitive to weak targets and have a more dynamic range—have better detection

BPQ

What is the benefit of signal amplification?

Intracellular Receptors

The ligand (primary messenger) passes through the cell membrane and forms a complex with an intracellular receptor in the cytoplasm or nucleus

Lactase Expression

Lactose forms a complex with Lac 9 which activates the expression of lactase

Gene expression allows lactase to only be made when it is needed (lactose is present)

BPQ

Why is lactase activity regulated by gene expression rather than kinase activity?

Ligand Gated Ion Channels

Ligand opens an ion channel

• Ion acts as a secondary messenger

Ca+ and Muscle Contraction

Ca+ acts as a secondary messenger, connecting an electrical impulse to muscle cell contractile proteins (sarcomeres)

Cell Surface Receptors

1. G Protein coupled receptors

2. Enzyme linked receptors

G Protein

consists of 3 subunits and a guanosine phosphate (GTP or GDP)

G Protein Coupled Receptors - Transduction process

1. G Protein with GDP associates with the receptor

2. Ligand binds

3. GDP is swapped with GTP

4. G protein subunits dissociates

5. Create downstream effects

Epinephrine Transduction in the Liver

Epinephrine leads to glycogen breakdown in liver

Enzyme linked receptors

receptors form dimers with phosphorylated tyrosine that can activate multiple proteins

Transduction Process

1. Inactive receptor

2. Ligand binds

3. Forms dimer with another receptor

4. Kinase phosphorylates tyrosine on the receptors

5. Intracellular proteins bind to phosphate docking sites

This receptor’s tyrosine dock inside the cell can interact with several enzymes once activated, allowing for many different types of responses. (???)

BPQ

Enzyme linked receptors are often responsible for the regulation of cell growth, proliferation, and differentiation. What aspect of these receptors make them well designed for such complex jobs?

“OR” Gate

• Some signal transduction pathways can be activated by different receptor ligand complexes

  • Logical ____

“AND” Gate

• Some signal transduction pathways require activation from two different receptor ligand complexes

  • Logical ____

Kinase

enzyme that adds a phosphate

Phosphatase

enzyme that removes a phosphate