Second messengers are intracellular signaling molecules released by the cell to trigger physiological changes such as
proliferation,
differentiation, migration, survival, and
apoptosis. Secondary messengers are therefore one of the initiating components of intracellular
signal transduction cascades. Examples of second messenger molecules include
cyclic AMP,
cyclic GMP,
inositol trisphosphate,
diacylglycerol, and
calcium. The cell releases second messenger molecules in response to exposure to extracellular signaling molecules—the
first messengers. First messengers are extracellular factors, often
hormones or
neurotransmitters, such as
epinephrine,
growth hormone, and
serotonin. Because
peptide hormones and neurotransmitters typically are biochemically
hydrophilic molecules, these first messengers may not physically cross the phospholipid bilayer
cell membrane to initiate changes within the cell directly—unlike
steroid hormones, which usually do. This functional limitation necessitates the cell to devise signal transduction mechanisms to transduce first messenger into second messengers, so that the extracellular signal may be propagated intracellularly. An important feature of the second messenger signaling system is that second messengers may be coupled downstream to multi-cyclic kinase cascades to greatly amplify the strength of the original first messenger signal. For example, Ras.GTP signals link with the Mitogen Activated Protein Kinase (MAPK) cascade to amplify the allosteric activation of proliferative transcription factors such as Myc and CREB.