Biosignaling
High-Yield Summary
- Three membrane protein categories carry biosignaling: ion channels, enzyme-linked receptors, and GPCRs.
- Ion channels move ions by facilitated diffusion (no ATP): ungated (always open), voltage-gated, or ligand-gated.
- Enzyme-linked receptors have 3 domains — membrane-spanning, ligand-binding, catalytic; classic example is receptor tyrosine kinase (RTK), which phosphorylates tyrosine residues on ligand binding (growth factors, insulin).
- GPCRs: ligand binds → G protein (α/β/γ) activates → α subunit swaps GDP for GTP → α separates from βγ to act on a target enzyme.
- Gs → stimulates adenylate cyclase → ↑cAMP → activates PKA. Gi → inhibits SAME enzyme → ↓cAMP (opposite effect, most commonly tested GPCR contrast).
- Gq → activates phospholipase C → cleaves PIP2 into DAG + IP3 → IP3 opens ER Ca²⁺ channels → ↑intracellular calcium.
Key Terms
- Facilitated diffusion
- Movement of ions/molecules down their concentration gradient through a channel, no energy required.
- Receptor tyrosine kinase (RTK)
- Enzyme-linked receptor whose catalytic domain phosphorylates tyrosine residues once activated by ligand.
- GPCR
- G protein-coupled receptor; ligand binding activates an associated G protein.
- cAMP
- Cyclic AMP; second messenger raised by Gs (via adenylate cyclase), activates protein kinase A (PKA).
- PIP2 / DAG / IP3
- Phospholipase C cleaves membrane lipid PIP2 into DAG and IP3; IP3 triggers ER calcium release.
Ion Channel Types
| Type | Trigger |
|---|---|
| Ungated | None — always open; movement depends only on concentration gradient |
| Voltage-gated | Change in membrane potential (key in neurons/muscle) |
| Ligand-gated | Binding of a specific ligand (neurotransmitter, hormone, etc.) |
Gs vs. Gi vs. Gq
| G Protein | Pathway & Effect |
|---|---|
| Gs | Stimulates adenylate cyclase → ↑cAMP → activates PKA |
| Gi | Inhibits adenylate cyclase (same enzyme as Gs) → ↓cAMP |
| Gq | Activates phospholipase C → PIP2 → DAG + IP3 → IP3 opens ER Ca²⁺ channels → ↑intracellular Ca²⁺ |
GPCR Activation Cascade
- 1Ligand binds the GPCR's extracellular domain.
- 2Receptor activates its associated G protein (α/β/γ trimer).
- 3α subunit exchanges bound GDP for GTP.
- 4GTP-bound α subunit dissociates from the βγ pair.
- 5Free α subunit activates (or inhibits) its target enzyme (adenylate cyclase or phospholipase C).
- 6Second messenger cascade proceeds (cAMP/PKA, or DAG+IP3/Ca²⁺).
Common MCAT Trap
- Gs and Gi act on the SAME enzyme (adenylate cyclase) with opposite effects — don't assume different G proteins always mean different target enzymes.
- Gq's pathway (phospholipase C/PIP2/DAG/IP3/Ca²⁺) is a completely separate system from the Gs/Gi cAMP pathway — don't cross-wire the two.
- Enzyme-linked receptors and GPCRs are both membrane proteins that respond to ligands, but only enzyme-linked receptors have an intrinsic catalytic domain — GPCRs act through a separate G protein intermediary.
Quick Recall
What are the three types of ion channels, by trigger?
What are the three domains of an enzyme-linked receptor?
What nucleotide exchange activates a G protein's alpha subunit?
Which G protein activates phospholipase C, and what two products does it generate from PIP2?