Cell signalling
Cell signalling

Start this free course now. Just create an account and sign in. Enrol and complete the course for a free statement of participation or digital badge if available.

3.4.2 Cyclic AMP

The concentration of cyclic AMP (cAMP) in the cytosol increases 20-fold within seconds of an appropriate stimulus. This is achieved by the action of the plasma membrane-embedded protein adenylyl cyclase, which synthesizes cAMP from ATP (Figure 34). cAMP is short-lived, as with all second messengers, because it is continuously degraded by cyclic AMP phosphodiesterases to 5′-AMP. Adenylyl cyclase is activated by stimulatory G proteins (Gαs) and inhibited indirectly by inhibitory G proteins (Gαi). It is usually the α subunit of the G protein that regulates adenylyl cyclase in this way, though sometimes the βγ complex can have the same effect. Different hormones can induce a similar cAMP response in a particular cell type, leading to similar cellular outcomes. However, different cell types will respond differently to similar cAMP increases, so the same hormone may have different effects on different cells. For example, cAMP mediates the action of adrenalin acting through β-adrenergic receptors (see Figure 48), causing glycogen breakdown in skeletal muscle cells, while promoting triglyceride breakdown in fat cells. Most of the downstream signals of cAMP are propagated by cAMP-dependent protein kinase A (PKA), which is a serine–threonine kinase.

Figure 34 The synthesis and degradation of cAMP. Adenylyl cyclase catalyses the formation of cAMP from ATP, removing the terminal two phosphates from ATP in the process. Removal of pyrophosphate (PPi) provides the energy for the cyclization reaction. cAMP is short-lived because it is rapidly hydrolysed by cAMP phosphodiesterase, yielding 5´-AMP.

PKA has many target proteins, which vary according to cell type. This explains why a hormone can produce the same increase in cAMP concentration in different cells, yet the cellular response to this increase is different for each cell type. PKA consists of two catalytic subunits and two regulatory subunits. The latter have two roles. They bind to PKA-anchoring proteins, thus tethering the enzyme to particular subcellular locations. They can also each bind two cAMP molecules in a cooperative fashion; when bound to more than two cAMP molecules, the regulatory subunits undergo sufficient conformational change for them to dissociate from the catalytic subunits (which remain in the cytosol). As with other signalling proteins with multiple binding sites, such as calmodulin, PKA is allosterically regulated by the second messenger cAMP. The released catalytic units are now active. They may act in the cytoplasm, for example by phosphorylating enzymes involved in glycogen metabolism and/or they may migrate to the nucleus, where they can switch on transcription of genes containing cAMP response elements (CREs) in their promoters. This is achieved by phosphorylating a serine on the nuclear CRE-binding protein (CREB), which, together with a coactivator, then binds to the CRE and stimulates transcription of the downstream gene.

Take your learning further

Making the decision to study can be a big step, which is why you'll want a trusted University. The Open University has 50 years’ experience delivering flexible learning and 170,000 students are studying with us right now. Take a look at all Open University courses.

If you are new to University-level study, we offer two introductory routes to our qualifications. You could either choose to start with an Access module, or a module which allows you to count your previous learning towards an Open University qualification. Read our guide on Where to take your learning next for more information.

Not ready for formal University study? Then browse over 1000 free courses on OpenLearn and sign up to our newsletter to hear about new free courses as they are released.

Every year, thousands of students decide to study with The Open University. With over 120 qualifications, we’ve got the right course for you.

Request an Open University prospectus371