Signal

The highest-yield point is to distinguish receptor types, their mechanisms, and their examples. This summary includes the diagrams and handwritten notes in your PDF.

Physiology - Signal transduction.pdf⁠

1. Types of cell communication

Type	Where does the signal act?	Key distinction
Endocrine	Distant target cells through blood	Hormones circulate widely; only cells with the appropriate receptor respond
Paracrine	Nearby cells	Local signaling
Autocrine	The same cell that released it	Self-signaling
Synaptic / neuronal	Target cell across a synaptic cleft	Neurotransmitter release; usually rapid and specific
Contact-dependent	An adjacent cell	Requires direct cell contact
Electrical	Adjacent cells through gap junctions	Direct passage of ionic current

2. Main receptor types — memorize this table

Receptor	Mechanism	Important examples
Intracellular receptor	Alters gene transcription → protein synthesis	Steroid hormones, thyroid hormones, vitamin D, retinoic acid
Ligand-gated ion channel	Ligand binding directly opens/closes an ion channel	Nicotinic ACh, GABA_A, glycine, 5-HT₃, ionotropic glutamate receptors
Receptor tyrosine kinase — RTK	Receptor has intrinsic kinase activity → phosphorylation	Insulin, many growth factors
JAK-associated receptor	Receptor activates a separate cytoplasmic kinase	Cytokines, erythropoietin, colony-stimulating factors; growth hormone
G protein–coupled receptor — GPCR	G protein activates an enzyme or ion channel	α₂-adrenergic receptor shown in the PDF

Key distinction: RTK = receptor itself is the kinase; JAK pathway = kinase is attached to the receptor.

3. Intracellular receptors

Basic pathway:

Lipid-soluble messenger → intracellular receptor → DNA regulation → mRNA → new protein → cellular response.

Receptors may be in the cytoplasm or nucleus.
These messengers commonly circulate bound to carrier proteins.
Effects mediated by gene expression generally have a slower onset and longer duration.

Messenger	What to remember
Steroid hormones	Derived from cholesterol: cortisol, aldosterone, testosterone, estrogen, progesterone
Thyroid hormones	Derived from tyrosine; receptors are nuclear and can already be bound to DNA
Vitamin D	Acts through a nuclear receptor
Retinoic acid	Vitamin A derivative; acts through nuclear receptors

Thyroid receptor diagram

Without hormone	With hormone
Receptor recruits corepressors + HDAC	Recruits coactivators + HAT
Chromatin becomes less accessible	Chromatin becomes more accessible
Transcription is repressed	Transcription is activated

HDAC: histone deacetylase → removes acetyl groups.
HAT: histone acetyltransferase → adds acetyl groups.

Estrogen receptor diagram: hormone binding → release of inhibitory heat-shock proteins → receptor dimerization → DNA binding → coactivator recruitment → transcription.

4. Ligand-gated ion channels

Ligand binds → channel opens → ions move → membrane potential and/or intracellular Ca²⁺ changes.

These produce very rapid responses.

Receptor	Main ion movement / effect
Nicotinic ACh	Cation movement → usually depolarization
GABA_A	Cl⁻ conductance → usually inhibition
Glycine	Cl⁻ conductance → usually inhibition
5-HT₃	Cation movement → excitation
AMPA / kainate	Glutamate-gated cation channels
NMDA	Glutamate receptor permeable to Ca²⁺ as well as other cations

Distinguish two mechanisms:

Extracellular ligand-gated channels: neurotransmitter binds directly to the channel.
Intracellular messenger-regulated channels: controlled by signals such as cGMP, cAMP, IP₃, or Ca²⁺.

The PDF associates cGMP with vision.

5. Receptor tyrosine kinases

Typical sequence:

Ligand binding → receptor dimerization/rearrangement → tyrosine autophosphorylation → signaling proteins dock → cellular response.

A kinase transfers phosphate from ATP to a protein.
Phosphorylated tyrosines provide docking sites for intracellular signaling proteins.
SH2 domains recognize phosphorylated tyrosines.
Insulin is the major hormone example.

PLC-γ pathway shown in the PDF:

Activated RTK → PLC-γ → PIP₂ splits into IP₃ + DAG

Second messenger	Main action
IP₃	Releases Ca²⁺ from the endoplasmic reticulum
DAG	Remains in the membrane and helps activate protein kinase C
Ca²⁺	Acts as an intracellular signal

6. JAK–STAT pathway

Ligand → receptor activation → JAK activation → STAT phosphorylation → STAT dimerization → nucleus → gene transcription.

JAK: Janus kinase.
STAT: signal transducer and activator of transcription.
The receptor does not possess intrinsic tyrosine kinase activity.
STAT directly connects membrane signaling to gene regulation.

Examples: cytokines, erythropoietin, colony-stimulating factors, and growth hormone.

7. G protein–coupled receptors

Associated with a G protein containing α, β, and γ subunits.
Activation causes GDP to be replaced by GTP on the α subunit.
Activated subunits regulate enzymes or ion channels.
GTP hydrolysis helps terminate the signal.

Example in your PDF: α₂-adrenergic receptor → Gᵢ → inhibition of adenylyl cyclase → ↓ cAMP.

Important corrections to the slides

Slide wording / annotation	Accurate point to memorize
Prostaglandins listed under intracellular receptors	Most prostaglandins act through cell-surface GPCRs
Growth hormone written beside RTKs	Growth hormone uses JAK–STAT; insulin uses an RTK
“GABA” and “5-HT” listed as ion-channel receptors	Specifically GABA_A and 5-HT₃; other subtypes use different mechanisms
Endocrine signaling described as nonspecific	Distribution is widespread, but responses are receptor-specific

Final recall:
Steroids/thyroid → intracellular receptors · Insulin → RTK · GH/EPO → JAK–STAT · Nicotinic ACh → ion channel · α₂ → Gᵢ → ↓ cAMP.