Editing Signal transduction (section)

===Intracellular receptors===
{{Main|Intracellular receptor}}

Intracellular receptors, such as [[nuclear receptor]]s and [[cytoplasm|cytoplasmic receptors]], are soluble proteins localized within their respective areas. The typical ligands for nuclear receptors are non-polar hormones like the [[steroid]] hormones [[testosterone]] and [[progesterone]] and derivatives of vitamins A and D. To initiate signal transduction, the ligand must pass through the plasma membrane by passive diffusion. On binding with the receptor, the ligands pass through the [[nuclear membrane]] into the [[cell nucleus|nucleus]], altering gene expression.

Activated nuclear receptors attach to the DNA at receptor-specific [[hormone response element|hormone-responsive element]] (HRE) sequences, located in the [[promotor (biology)|promoter]] region of the genes activated by the hormone-receptor complex. Due to their enabling gene transcription, they are alternatively called inductors of [[gene expression]]. All hormones that act by regulation of gene expression have two consequences in their mechanism of action; their effects are produced after a characteristically long period of time and their effects persist for another long period of time, even after their concentration has been reduced to zero, due to a relatively slow turnover of most enzymes and proteins that would either deactivate or terminate ligand binding onto the receptor.

Nucleic receptors have DNA-binding domains containing [[zinc finger]]s and a ligand-binding domain; the zinc fingers stabilize DNA binding by holding its phosphate backbone. DNA sequences that match the receptor are usually hexameric repeats of any kind; the sequences are similar but their orientation and distance differentiate them. The ligand-binding domain is additionally responsible for [[protein dimer|dimerization]] of nucleic receptors prior to binding and providing structures for [[transactivation]] used for communication with the translational apparatus.

[[Steroid receptor]]s are a subclass of nuclear receptors located primarily within the cytosol. In the absence of steroids, they associate in an aporeceptor complex containing [[chaperone protein|chaperone]] or [[heatshock protein]]s (HSPs). The HSPs are necessary to activate the receptor by assisting the protein to [[protein folding|fold]] in a way such that the [[signal peptide|signal sequence]] enabling its passage into the nucleus is accessible. Steroid receptors, on the other hand, may be repressive on gene expression when their transactivation domain is hidden. Receptor activity can be enhanced by phosphorylation of [[serine]] residues at their N-terminal as a result of another signal transduction pathway, a process called [[crosstalk (biology)|crosstalk]].

[[Retinoic acid receptor]]s are another subset of nuclear receptors. They can be activated by an endocrine-synthesized ligand that entered the cell by diffusion, a ligand synthesised from a [[Protein precursor|precursor]] like [[retinol]] brought to the cell through the bloodstream or a completely intracellularly synthesised ligand like [[prostaglandin]]. These receptors are located in the nucleus and are not accompanied by HSPs. They repress their gene by binding to their specific DNA sequence when no ligand binds to them, and vice versa.

Certain intracellular receptors of the immune system are cytoplasmic receptors; recently identified [[Pattern recognition receptor|NOD-like receptors]] (NLRs) reside in the cytoplasm of some [[eukaryotic]] cells and interact with ligands using a [[leucine-rich repeat]] (LRR) motif similar to TLRs. Some of these molecules like [[NOD2]] interact with [[RIPK2|RIP2 kinase]] that activates [[NF-κB]] signaling, whereas others like [[NALP3]] interact with inflammatory [[caspase]]s and initiate processing of particular [[cytokine]]s like [[interleukin-1]]β.<ref>{{Cite journal |vauthors=Delbridge LM, O'Riordan MX |date=February 2007 |title=Innate recognition of intracellular bacteria |journal=Current Opinion in Immunology |volume=19 |issue=1 |pages=10–6 |doi=10.1016/j.coi.2006.11.005 |pmid=17126540}}</ref><ref name="Vander_1998" />