Second Messengers

Second messengers are molecules that relay signals received at receptors on the cell surface — such as the arrival of protein hormones, growth factors, etc. — to target molecules in the cytosol and/or nucleus.

But in addition to their job as relay molecules, second messengers serve to greatly amplify the strength of the signal. Binding of a ligand to a single receptor at the cell surface may end up causing massive changes in the biochemical activities within the cell.

There are 3 major classes of second messengers:
  1. cyclic nucleotides (e.g., cAMP and cGMP)
  2. inositol trisphosphate (IP3) and diacylglycerol (DAG)
  3. calcium ions (Ca2+)

Cyclic Nucleotides

Cyclic AMP (cAMP)

Some of the hormones that achieve their effects through cAMP as a second messenger: Cyclic AMP is synthesized from ATP by the action of the enzyme adenylyl cyclase.

Cyclic GMP (cGMP)

Cyclic GMP is synthesized from the nucleotide GTP using the enzyme guanylyl cyclase.

Cyclic GMP serves as the second messenger for

Some of the effects of cGMP are mediated through Protein Kinase G (PKG) — a cGMP-dependent protein kinase that phosphorylates target proteins in the cell.

Inositol trisphosphate (IP3) and diacylglycerol (DAG)

Peptide and protein hormones like and neurotransmitters like GABA
bind to G protein-coupled receptors (GPCRs) that activate the intracellular enzyme phospholipase C (PLC).

As its name suggests, it hydrolyzes phospholipids — specifically phosphatidylinositol-4,5-bisphosphate (PIP2) which is found in the inner layer of the plasma membrane. Hydrolysis of PIP2 yields two products:

The binding of an antigen to its receptor on a B cell (the BCR) also generates the second messengers DAG and IP3.

Calcium ions (Ca2+)

As the functions of IP3 and DAG indicate, calcium ions are also important intracellular messengers. In fact, calcium ions are probably the most widely used intracellular messengers.

In response to many different signals, a rise in the concentration of Ca2+ in the cytosol triggers many types of events such as Normally, the level of calcium in the cell is very low (~100 nM). There are two main depots of Ca2+ for the cell: However, its level in the cell can rise dramatically

Getting Ca2+ into (and out of) the cytosol

Ca2+ ions are returned

How can such a simple ion like Ca2+ regulate so many different processes? Some factors at work:

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8 April 2011