second messengers

Second messenger

a small molecule that relays a signal from a cell-surface receptor to a target inside the cell, amplifying the signal in the process

Features of second messengers

small and highly mobile, non-protein (lipid-derived), can be made/ released in large numbers

Examples of second messengers

Ca2+, cAMP

How are cytosolic Ca2+ levels controlled?

by balance between release/ entry and removal from cytosol

cAMP

Synthesised by adenylyl cyclase; degraded by cAMP phosphodiesterase; located intracellularly; activated by GPCRs; targets kinases, channels, and GEFs.

cGMP

Synthesised by guanylyl cyclase; degraded by cGMP phosphodiesterase; located intracellularly; activated by nitric oxide, rhodopsin, and receptor guanylate cyclase; targets kinases and channels.

Inositol triphosphate (IP₃)

Synthesised by phospholipase C (PLC); eliminated by dephosphorylation; intracellular; activated by receptor tyrosine kinases and GPCRs; targets IP₃ receptors.

Diacylglycerol (DAG)

Synthesised by phospholipase C (PLC); eliminated by phosphorylation; membrane-restricted; activated by receptor tyrosine kinases and GPCRs; targets kinases.

Phosphoinositides (e.g., PIP₂)

Synthesised by PI kinase; eliminated by PI phosphatases; membrane-restricted; activated by receptor tyrosine kinases and GPCRs; targets kinases and many PH-domain proteins.

Ca²⁺

Released from intracellular stores via Ca²⁺ channels; removed via Ca²⁺-ATPase pumps and Ca²⁺-sequestering proteins; intracellular; stimulated by channels and IP₃; targets kinases, enzymes, calmodulin, cytoskeletal proteins.

Nitric oxide (NO)

Synthesised by nitric oxide synthase; eliminated by reaction with O₂/Hb; intercellular/intracellular; activated by Ca²⁺/calmodulin, neurotransmitters; targets guanylyl cyclase.