Cell Signaling and Signal Transduction Pathways

Receptors

Insulin is a peptide hormone (dimer).
Testosterone is a hydrophobic signal that passes through the plasma membrane; receptors are internal.
Receptor tyrosine kinases dimerize before relaying a signal.
Gated ion channels require a signal to open.
Receptor tyrosine kinases activate multiple relay molecules.

Direct the response to the appropriate target.
Provide an opportunity to amplify the signal.
Occur in animals and plants.
Signal reception may lead to multiple metabolic effects.
Cells without receptors do not respond to the signal.
Signal transduction occurs inside cells and involves multiple steps like protein phosphorylation mediated by protein kinases.
Amplification of the signal is a key concept.
Turning off the signal is crucial; many diseases involve failures in turning off these pathways.
Many pharmaceutical drugs target signal transduction receptors.
Generic Pathway:
- Signal molecule binds to a receptor.
- Leads to a relay molecule.
- Activates an inactive protein kinase, setting up a phosphorylation cascade.
- Each step allows for amplification of the signal.
- Phosphatases catalyze the removal of phosphate groups, restoring proteins to their inactive form.
Second messengers are often involved.
- Example: Epinephrine (adrenaline) binds to a G protein-linked receptor.
- Activates a G protein, which activates adenylyl cyclase.
- Adenylyl cyclase cyclizes ATP into cyclic AMP (cAMP).
- cAMP activates a protein kinase.

Involves cytoplasmic activities or changes in gene transcription.
Hormones and growth factors: chemical signals that bind to protein receptors.
Effects can be rapid (seconds/minutes) or slow (hours/days).
Rapid Effects:
- Glucagon binds to receptors on liver cells, altering enzymatic activity to release glucose.
- Epinephrine is released from adrenal glands, boosting glucose supply during stress, via a G protein-linked receptor and secondary messenger cAMP.
Homeostasis (Blood Glucose Levels):
- Insulin (released by beta cells in the pancreas) enables cells to take up glucose and activates glucose storage as glycogen, lowering blood glucose.
- Glucagon (released by alpha cells) activates the release of glucose from glycogen, raising blood glucose.
- Type 2 diabetes results from overstimulation of the pancreas, leading to reduced insulin response and high glucose levels.
Cytoplasmic Responses (Epinephrine Example):
- One molecule of epinephrine at the receptor can lead to millions of glucose molecules through signal amplification.
Hormonal Effects (Slower): Alter gene expression and protein synthesis.
- Growth factors bind to receptors, leading to a phosphorylation cascade targeting transcription factors.
- Active transcription factors dimerize, bind to DNA, and switch on genes.

Signal reception may lead to multiple metabolic effects.
The same receptor and signal in different cells can lead to different responses.
Cells without receptors do not respond to a signal.
Multiple signaling pathways allow a specific cell response to be controlled by many signals.
Signals need to be turned off.
Different receptors on different cell types, with varied relay proteins and signal transduction pathways, diversify responses.