The signals may be environmental factors like light or they may be signals produced by other cells.
Signals from other cells are especially important in complex multicellular
organisms, like humans, where they integrate and coordinate the functions
of the individual cells for the benefit of the whole organism.
In complex multicellular organisms cell-cell signaling can be divided into 3 general categories depending on the distance over which the signal is transmitted: (Fig. 13.1)
But a cell will only respond to a signal, if it is able to perceive the signal. This is accomplished via receptors which are proteins that specifically bind signal molecules.
Another prerequisit for response to a signal is the ability of the activated receptor (the receptor that has bound a signal molecule) to induce some kind of intracellular reaction that leads to the response behavior.
Many receptors are located at the cell surface, but some
are localized inside the cell (intracellular).
An example for intracellular receptors are the steroid hormone receptors. They respond to steroid hormones like the sex hormone estrogen but there are also many other sex or non-sex steroid hormones. By the way the name steroid hormones already indicates endocrine signaling.
Because steroid hormones are small, hydrophobic molecules they can cross the plasma membrane which allows them to bind to their intracellular receptors.
All steroid hormone receptors act as transcription factors therefore directly influencing gene transcription. For example the estrogen receptor cannot bind DNA in the absence of the hormone. Binding of estrogen induces a conformational change in the receptor allowing it to bind to specific regulatory DNA sequences and therefore to activate transcription of certain genes as a response.
If the signaling molecule is hydrophilic it cannot cross the plasma membrane but its receptor will be located at the cell surface. Cell-surface receptors are membrane-spanning proteins that protrude into the cell exterior with their signal-binding domains.
The location of cell-surface receptors makes it necessary to transmit
the signal from the plasma membrane (the activated receptor) to other parts
of the cell. The information from a first messenger (an intercellular
signal, here the hormone) is transmitted to a second messenger (an
intracellular signal).
In order to understand the concept of second messenger we will discuss it with a specific example:
The action of the hormone epinephrine on muscle cells in mammals.
The hormone's effect on muscle cells is a rise in intracellular glucose concentration providing energy in antissipation of increased mucle activity. This becomes necessary for example when sudden flight seems required.
1. Epinephrine (the first messenger, also called adrenaline) is excreted
from specialized cells, carried with the blood stream and eventually arrives
at the muscle cells.
2. Here it binds to its specific receptor (Fig. 13.12). The epinephrine receptor belongs to a large family of cell-surface receptors called G protein-coupled receptors. When activated they all transmit their signal via the activation of the small guanosine nucleotide-binding protein called G protein. G protein in its inactive state has bound a GDP. The activated epinephrine receptor exchanges the GDP in the G protein for a GTP. This causes the G protein to undergo transformation into its active state.
3. In muscle cells (Fig. 13.11) the activated G protein in turn will activate an enzyme called adenylyl cyclase which like the epinephrine receptor is also localized in the plasma membrane. The enzyme catalyzes the formation of cyclic AMP (cAMP) from ATP. cAMP is a second messenger that carries the signal from the plasma membrane to the interior of the cell. cAMP also acts as second messenger in many other cells and other intracellular signal transductions.
(Structure of phosphate and ribose in cAMP to show its cyclic nature, Fig. 13.18)
4. The activity of adenylyl cyclase leads to a rise in cAMP concentration. This high cAMP concentration in turn leads to the next step in intracellular signal transduction: the activation of the cAMP-dependent protein kinase or protein kinase A (Fig. 13.19).
5. As the name says, protein kinase A can phosphorylate
proteins. It specifically phosphorylates two proteins in muscle cells (Fig.
13.20):
glycogen synthase which becomes inactive and therefore will
not use glucose anymore to synthesize glycogen,
and glycogen phosphorylase kinase, another protein kinase which
is activated upon phosphorylation.
Active glycogen phosphorylase kinase acts, as its name says, by specifically
phosphorylating the enzyme glycogen phosphorylase. This leads to
an activation of glycogen phosphorylase which will catalyze the breakdown
of glycogen to glucose.
Epinephrine, via protein kinase A, therefore acts two-fold to increase glucose concentrations in the muscle cell: it induces the activation of the enzyme that produces glucose from the storage molecule glycogen (glycogen phosphorylase) and it induces the inhibition of the enzyme that consumes glucose to form glycogen (glycogen synthase).
Phosphorylation of a protein via a protein kinase is a frequent
step in intracellular signal transduction. The reaction can even be arranged
in whole phosphorylation cascades where one protein kinase phosphorylates
another which in turn phosphorylates another and so on.