Cell Signaling Pathways: EGF, Ras, Estrogen, and Glucagon Mechanisms

What is Epidermal Growth Factor (EGF)?

A peptide hormone (53 amino acids) that acts as a paracrine signal and pushes cells from G0 → G1.

What type of receptor is the EGF receptor (EGF-R)?

A receptor tyrosine kinase (RTK) that spans the membrane.

What happens when EGF binds EGF-R?

The receptors dimerize (homodimer) and activate each other.

What is cross-phosphorylation?

Each EGF receptor phosphorylates the other.

What binds to phosphorylated EGF-R?

The Grb2/SOS protein complex.

What is the role of SOS?

It acts as a GEF (Guanine Exchange Factor) for Ras.

What kind of protein is Ras?

A small G protein that acts as a molecular switch.

When is Ras active vs inactive?

Active = GTP bound; Inactive = GDP bound.

What does GEF do?

Exchanges GDP for GTP to activate Ras.

What does GAP do?

Turns Ras off by converting GTP → GDP.

What does activated Ras do?

Activates Raf (a kinase).

What is the kinase cascade order?

Raf → MEK → ERK.

Why is a kinase cascade important?

Signal amplification (one signal becomes many).

What does ERK do when activated?

Phosphorylates transcription factors like Elk-1.

What happens to Elk-1 after phosphorylation?

It enters the nucleus.

What gene is activated by Elk-1?

Cyclin D.

What does Cyclin D do?

Pushes the cell past the restriction point → cell growth.

How is EGF signaling turned off?

EGF degraded, phosphatases remove phosphates, Ras inactivated by GAP, Cyclin D degraded, Grb2/SOS leaves membrane.

Why is turning off the pathway important?

Prevents uncontrolled cell growth (cancer).

What happens with Ras mutations?

Ras stays active (can't hydrolyze GTP).

What is a common Raf mutation?

V600E → always active kinase.

What happens with mutated EGF receptors?

They dimerize without ligand → constant signaling.

What type of hormone is estrogen?

A steroid hormone (hydrophobic).

Where is the estrogen receptor (ER)?

In the cytosol.

What happens when estrogen binds ER?

It changes shape and enters the nucleus.

What does ER do in the nucleus?

Binds DNA and activates gene transcription.

What type of receptor does glucagon use?

GPCR (G protein-coupled receptor).

What G protein is involved here?

Gq.

What enzyme does Gq activate?

Phospholipase C (PLC).

What does PLC do?

Cuts PIP2 into DAG and IP3.

What is IP3?

A second messenger.

What does IP3 do?

Releases Ca²⁺ from the ER.

What role does Ca²⁺ play?

Acts as a second messenger.

What are second messengers?

Small molecules that relay signals inside the cell (e.g., IP3, Ca²⁺).

Are signaling pathways simple ON/OFF?

No, they are dynamic and influenced by multiple factors.