4. Autocrine Signaling

• Cell signals itself
• Important in development and immune response

Reception

Receptors: Proteins that bind signal molecules (ligands)

Types:

1. Cell Surface Receptors

• For hydrophilic signals (can't cross membrane)
• G protein-coupled receptors (GPCRs)
• Receptor tyrosine kinases (RTKs)
• Ligand-gated ion channels

2. Intracellular Receptors

• For hydrophobic signals (can cross membrane)
• Located in cytoplasm or nucleus
• Examples: steroid hormones, thyroid hormones

Signal Transduction

Transduction: Converting signal into cellular response

Key mechanisms:

1. Protein Phosphorylation Cascades

• Protein kinases add phosphate groups
• Protein phosphatases remove phosphate groups
• Phosphorylation relay: chain of activated proteins
• Amplifies signal

2. Second Messengers

Small molecules that relay signals inside cell:

cAMP (cyclic AMP):

• Made from ATP by adenylyl cyclase
• Activates protein kinase A (PKA)
• Degraded by phosphodiesterase

Ca²⁺ (calcium ions):

• Stored in ER, released into cytoplasm
• Activates many proteins
• Important in muscle contraction, neurotransmitter release

IP₃ and DAG:

• Made from membrane phospholipids
• IP₃ triggers Ca²⁺ release
• DAG activates protein kinase C (PKC)

3. Signal Amplification

• One signal molecule activates many molecules
• Cascade effect
• Example: 1 epinephrine → billions of glucose molecules released

Response

Cellular responses:

• Gene expression changes
• Enzyme activation/inhibition
• Cell shape/movement changes
• Cell division
• Apoptosis (programmed cell death)

Regulation of Signaling

Termination mechanisms:

• Ligand dissociates from receptor
• Receptor inactivated or degraded
• Second messengers broken down
• Protein phosphatases remove phosphate groups

Feedback mechanisms:

• Negative feedback: response inhibits pathway
• Positive feedback: response enhances pathway

Key Concepts

1. Three stages: reception, transduction, response
2. Cell surface receptors for hydrophilic signals
3. Intracellular receptors for hydrophobic signals
4. Phosphorylation cascades transmit and amplify signals
5. Second messengers (cAMP, Ca²⁺) relay signals
6. Signal amplification allows small stimulus → large response
7. Feedback regulation controls signaling pathways