All cells receive and respond to signals from their surroundings.

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)

endocrine signaling: the signal molecule is secreted by specialized endocrine cells, carried over far distances with the circulatory system, and finally is perceived by target cells far away from the signal-producing cells. Such signaling molecules are called hormones, per definition signal molecules that act over great distances. paracrine signaling: the signal molecule acts locally on neighboring cells. The signal molecule might not even be released into the extracellular fluid by the signal-producing cell but rather expressed on its surface (direct cell-to-cell signaling). autocrine signaling: the signaling molecule acts on the signal-producing cell itself inducing it to respond.

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.

Cell-surface receptors are membranespanning 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. This becomes necessary for example when sudden flight seems required. also called adrenaline) is excreted from specialized cells. When activated they all transmit their signal via the activation of the small guanosine nucleotide-binding protein called G protein. carried with the blood stream and eventually arrives at the muscle cells. here the hormone) is transmitted to a second messenger (an intracellular signal). The epinephrine receptor belongs to a large family of cell-surface receptors calledG protein-coupled receptors. 2. 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. hydrophobic molecules they can cross the plasma membrane which allows them to bind to their intracellular receptors. G protein in its inactive state has bound a GDP. . Here it binds to its specific receptor (Fig. All steroid hormone receptors act as transcription factors therefore directly influencing gene transcription. The hormone's effect on muscle cells is a rise in intracellular glucose concentration providing energy in antissipation of increased mucle activity. 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.Because steroid hormones are small. If the signaling molecule is hydrophilic it cannot cross the plasma membrane but its receptor will be located at the cell surface. 1. 13. Epinephrine (the first messenger.12). The information from a first messenger (an intercellular signal. 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.

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. 13. 13. by specifically phosphorylating the enzyme glycogen phosphorylase. (Structure of phosphate and ribose in cAMP to show its cyclic nature.20): glycogen synthase which becomes inactive and therefore will not use glucose anymore to synthesize glycogen. cAMP also acts as second messenger in many other cells and other intracellular signal transductions. . Phosphorylation of a protein via a protein kinase is a frequent step in intracellular signal transduction.3. It specifically phosphorylates two proteins in muscle cells (Fig. as its name says. As the name says. Fig. another protein kinase which is activated upon phosphorylation. 5. In muscle cells (Fig. 13. 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).19). 13. via protein kinase A.18) 4. and glycogen phosphorylase kinase. protein kinase A can phosphorylate proteins. 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. This leads to an activation of glycogen phosphorylase which will catalyze the breakdown of glycogen to glucose. Active glycogen phosphorylase kinase acts.cAMP is a second messenger that carries the signal from the plasma membrane to the interior of the cell. Epinephrine. The enzyme catalyzes the formation of cyclic AMP (cAMP) from ATP. The activity of adenylyl cyclase leads to a rise in cAMP concentration. The reaction can even be arranged in whole phosphorylation cascades where one protein kinase phosphorylates another which in turn phosphorylates another and so on.