Signaling cascade

Jeffery Li

Ion channel coupled signalling: This type of signaling is mediated by a small number of
neurotransmitters that transiently open or close an ion channel formed by the protein to which
they bind, briefly changing the ion permeability of the plasma membrane and thereby
changing the excitability of the postsynaptic target cell.

Enzyme coupled signalling: Enzyme-coupled receptors either function as enzymes or associate

There are three type directly with enzymes that they activate. They are usually single-pass transmembrane proteins
of membrane signaling that have their ligand-binding site outside the cell and their catalytic or enzyme-binding site
inside.

G protein couple signalling: G-protein-coupled receptors act by indirectly regulating the

activity of a separate plasma-membrane-bound target protein, which is generally either an
enzyme or an ion channel, which is done by mediating the interaction between the activated
receptor and this target protein and further altering the concentration of intracellular signal
molecules that alter other protein.

receptor tyrosine kinases (RTKs): It is a type of enzyme-coupled receptor

which transport signal by activating the phosphorylation to generate
binding site to initiate second messenger. An example of this is insulin
receptor in liver which montain thousands of RTK on the liver cell
membranes. The metabolism is very clear that the signal protein binds to
the extracellular ligand domian and activates the dimerisation of the two
manomers of RTK so does the phosphorylation of tryosin domain of the
RTK inside the cell to generate docking site for the intracellular signling
complex.

Mechanisms of G protein coupled receptor

Most of the signaling process are activated or inactivated by

phosphorylation of ADP or hydrolysis of ATP by protein kinase or
phosphatase. However, G protein utilizes GTP as an alternative of energy
source regulated by GTPase activating protein which increase the rate of
hydrolysis of GTP to GDP while Guanine nucleotide exchange factor which
promote the release of GDP to allow new GTP to bind.

G protein and second messenger

The most well studied second messenger initiate by G protein receptor is

cyclic AMP (cAMP) whose concentration can be increased for twenty
folds after activation of G protein coupled receptor(GPCR). Then cAMP
can activate cyclic AMP dependent protein kinase(PKA) which then
phosphorylate the serine or threonine, regulating the protein activity.
cAMP may even regulate genetic transcription by activating the cyclic
nd
AMP response element(CRE). There are also other types of 2 messenger
such as IP2 and IP3, raising the concentration of the calcium ion in the
cytosol from though ER, which may cause membrane depolarization in
nerve cell.

Reference:Alberts, Johnson, (2010). Molecular bilogy of the cell sixth edition. Garland Science publisher.