Cell Signaling and Signal Transduction

How cells communicate through chemical signals and receptors

📡 Cell Signaling and Signal Transduction

Overview

Cell signaling: How cells communicate and respond to their environment

Three stages:

Reception: Signal molecule binds to receptor
Transduction: Signal converted into cellular response
Response: Cell changes behavior

Types of Cell Signaling

1. Direct Contact

Gap junctions: channels between animal cells
Plasmodesmata: channels between plant cells
Cell surface markers: immune recognition

2. Paracrine Signaling

Local signaling to nearby cells
Short-distance diffusion
Example: growth factors, neurotransmitters

3. Endocrine Signaling

Long-distance via bloodstream
Hormones travel throughout body
Example: insulin, estrogen, testosterone

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

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

📚 Practice Problems

1Problem 1medium

❓ Question:

Describe the three stages of cell signaling: (a) reception, (b) transduction, and (c) response. Use the epinephrine (adrenaline) signaling pathway as a specific example, explaining signal amplification.

💡 Show Solution

Cell Signaling - Three Stages:

(a) Reception:

Definition: Signal molecule binds to receptor protein

Epinephrine example:

Signal molecule: Epinephrine (hormone)
Receptor: G-protein-coupled receptor (GPCR) on liver cell membrane
Location: Extracellular surface of plasma membrane
Epinephrine cannot cross membrane (hydrophilic)

Specificity:

Only cells with epinephrine receptors respond
Different receptors (α, β) → different responses

(b) Transduction:

Definition: Signal converted to form that brings about cellular response

Epinephrine pathway (simplified):

Step 1: Epinephrine binds → receptor changes shape

Step 2: Activated receptor activates G protein

G protein exchanges GDP for GTP
G protein dissociates, activated

Step 3: G protein activates adenylyl cyclase (enzyme in membrane)

Step 4: Adenylyl cyclase converts ATP → cAMP (second messenger) $\text{ATP} \xrightarrow{\text{adenylyl cyclase}} \text{cAMP} + \text{PP}_i$

Step 5: cAMP activates protein kinase A (PKA)

PKA normally inactive (regulatory + catalytic subunits)
cAMP binds regulatory subunits → releases catalytic subunits
Active PKA phosphorylates target proteins

Step 6: PKA activates phosphorylase kinase

Step 7: Phosphorylase kinase activates glycogen phosphorylase

(c) Response:

Definition: Transduced signal triggers specific cellular response

Epinephrine response:

Final enzyme: Glycogen phosphorylase $\text{Glycogen} \xrightarrow{\text{phosphorylase}} \text{Glucose-1-phosphate} \rightarrow \text{Glucose}$

Cellular response:

Glycogen breakdown increases
Glucose released into bloodstream
Energy available for "fight or flight"

Signal Amplification:

Cascade effect - each step amplifies signal:

1 epinephrine molecule
    ↓
~100 G proteins activated
    ↓
~1,000 adenylyl cyclase molecules activated
    ↓
~10,000 cAMP molecules produced
    ↓
~10,000 PKA activated
    ↓
~100,000 phosphorylase kinase activated
    ↓
~1,000,000 glycogen phosphorylase activated
    ↓
~100,000,000 glucose molecules released!

Amplification factor: ~10⁸-fold (100 million)!

$\boxed{\text{1 signal molecule} \rightarrow 10^8 \text{ response molecules}}$

Termination:

cAMP broken down by phosphodiesterase
Removes second messenger
PKA inactivated
Signal stops

Why amplification matters:

Small amount of hormone → large response
Efficient use of signal molecules
Allows rapid, massive cellular response

Other examples:

Insulin: Promotes glucose uptake (tyrosine kinase receptor)
Growth factors: Cell division (receptor tyrosine kinases)
Neurotransmitters: Nerve impulse transmission (ligand-gated ion channels)

2Problem 2medium