3.5 Signal Transduction
Signal transduction cascades amplify and convert receptor activation into cellular responses. Understanding these pathways reveals drug targets and mechanisms.
G-Protein Signaling
Gs (Stimulatory)
Activates adenylyl cyclase โ โcAMP โ PKA activation. ฮฒ-adrenergic receptors.
Gi (Inhibitory)
Inhibits adenylyl cyclase โ โcAMP. ฮผ-opioid, ฮฑ2-adrenergic, M2 muscarinic.
Gq
Activates PLC โ IP3 + DAG โ Ca2+ release + PKC. ฮฑ1-adrenergic, M1/M3 muscarinic.
Second Messengers
cAMP
Activates PKA, EPAC. Degraded by phosphodiesterases (PDE target: sildenafil).
IP3/DAG
IP3 releases ER calcium. DAG activates PKC. From PIP2 hydrolysis.
Calcium
Universal messenger. Activates calmodulin, kinases, exocytosis.
cGMP
NO โ guanylyl cyclase โ cGMP โ PKG. Smooth muscle relaxation.
Kinase Cascades
MAPK Pathway
Ras โ Raf โ MEK โ ERK. Growth, differentiation, survival. Cancer drug targets.
PI3K/Akt
Survival, metabolism, growth. Insulin signaling. mTOR downstream.
JAK/STAT
Cytokine receptors. Gene transcription. JAK inhibitors for autoimmune disease.