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three stages of cell signaling
reception, transduction, response
reception
ligand binds a specific receptor
transduction
signal is relayed/amplified through a pathway
response
specific cellular outcome: gene expression, metabolic change, or altered membrane potential
signaling range
local signaling vs long distance signaling
local signaling
paracrine — diffusing short distances to nearby cells; synaptic — across a synapse via neurotransmitters
long distance signaling
endocrine/hormonal — hormones travel through the circulatory system to distant target cells
water soluble signals (peptide, hormones, epinephrine) can’t…
… cross the membrane, so they bind surface receptors (GPCRs, RTKs, ligand-gated ion channels)
lipid soluble/small signals (steroid/thyroid hormones) can…
…cross the membrane directly and bind intracellular receptors, often acting as transcription factors
four receptor types
GPCR, ligand gated ion channels, intracellular receptors
GPCR
use a G protein + GTP to relay the signal
RTK
dimerize and autophosphorylate, can trigger multiple pathways at once
ligand gated ion channels
open/close to let specific ions flow
intracellular receptors
bind lipid-soluble signals, directly regulate gene expression
signal transduction
relies heavily on phosphorylation cascades: kinases add a phosphate from ATP (usually activating a protein); phosphatases remove a phosphate (usually inactivating it) — this is a widespread, reversible on/off switch mechanism
second messengers (like cAMP, made from ATP by adenylyl cyclase)
rapidly spread a signal throughout the cell. Amplification happens because each activated molecule can activate many more molecules at the next step, producing an exponential (geometric) increase — a single signal molecule can ultimately affect hundreds of millions of downstream molecules
specificity
comes from each cell type's unique collection of receptors and relay proteins — the same signal (e.g., epinephrine) can produce different, even opposite, effects in different target cells
signal termination is essential because
falling ligand concentration lets receptors revert to inactive; phosphatases remove activating phosphates; phosphodiesterase breaks down cAMP into AMP, shutting off that part of the cascade