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.

2.5 Intracellular receptors

Signal receptors are usually located at the cell surface. However, it is important to remember that there are some groups of receptors that do not fit into the general signal transduction model set out in Figure 2, These are intracellular receptors, which bind small or lipophilic molecules such as steroid hormones, which can cross the cell membrane. The signalling pathways activated by these receptors seem quite simple compared with the other pathways we shall be dealing with, but the same principles of ligand binding, conformational change, signal amplification, translocation and so on described earlier still apply.

One important family of intracellular receptors are the nuclear receptors (also known as ‘nuclear hormone receptors’), which includes receptors for steroid hormones, thyroid hormones, retinoids and vitamin D. Although the ligands differ in their structural type, all nuclear receptors are structurally similar. They are good examples of receptors with intrinsic transcriptional activity (Section 1.3), comprising a transcription-activating domain, a DNA-binding domain and a ligand-binding domain. Their ligands are all small and hydrophobic, and so they can diffuse readily through the plasma membrane. The receptors are usually held in an inactive conformation by inhibitory proteins (often chaperones/heat-shock proteins). Binding of the ligand induces a conformational change that causes the inhibitory protein to dissociate from the receptor (Figure 27). The receptor may then translocate to the nucleus if it was in the cytoplasm, or it may already be in the nucleus; either way, the receptor–ligand complex is now able to bind to specific DNA sequences by means of its DNA-binding domain. Binding to DNA can also be facilitated by association of the receptor–ligand complex with other proteins (referred to as ‘coactivator proteins’). The DNA sequence to which the receptor–ligand complex binds is a promoter region of the target genes; in the case of hormones, it is called a ‘hormone response element (HRE)’.

Figure 27 The mechanism of nuclear receptor activation. (a) The inactive receptor, bound to an inhibitory protein. (b) In the receptor, ligand binding induces the ligand-binding domain to shut tight around the ligand, allowing the inhibitory protein to leave the complex. This allows the binding of a coactivator protein and consequent binding to a hormone response element in the DNA sequence, and initiating gene transcription.

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