Signal Transduction

Once a receptor is activated, the signal is usually transduced through a series of molecular changes rather than acted on directly. The most common mechanism is a phosphorylation cascade: an activated protein kinase phosphorylates the next kinase in line, which becomes active and phosphorylates the next, and so on.

Because each activated kinase can phosphorylate many copies of the next protein, cascades massively amplify the original signal - a single bound ligand can ultimately activate thousands of downstream molecules, allowing a small, transient signal at the membrane to produce a large, rapid change inside the cell.

Second messengers are small, water-soluble, non-protein molecules or ions that diffuse rapidly through the cytoplasm, broadcasting a signal from the plasma membrane to targets throughout the cell. Common examples include cyclic AMP (cAMP), produced from ATP by adenylyl cyclase downstream of many activated GPCRs; inositol trisphosphate (IP₃) and diacylglycerol (DAG), produced by cleavage of a membrane phospholipid; and calcium ions (Ca²⁺), released from the endoplasmic reticulum in response to IP₃.

Because second messengers are small and diffuse quickly, they can reach targets throughout the cell far faster than a protein could, and one second-messenger-producing enzyme can generate large numbers of second-messenger molecules, adding another layer of amplification to the pathway.

Signal transduction pathways must be reversible so cells can respond to changing conditions. Protein phosphatases remove phosphate groups added by kinases, GTPase activity built into G-proteins hydrolyzes bound GTP back to GDP to turn G-proteins off, and enzymes such as phosphodiesterase rapidly degrade second messengers like cAMP.

This tight regulation ensures the amplitude and duration of a response matches the strength and duration of the original signal, and prevents pathways from remaining locked in an 'on' state, which would be damaging or lead to uncontrolled cell behavior.