GPR31

Key takeaways

GPR31 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect GPR31 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of GPR31 from memory before moving on to harder problems.

Reference excerpt

G-protein coupled receptor 31 also known as 12-(S)-HETE receptor is a protein that in humans is encoded by the GPR31 gene. The human gene is located on chromosome 6q27 and encodes a G-protein coupled receptor protein composed of 319 amino acids.

Function The GPR31 receptor shares a close amino acid sequence similarity with the oxoeicosanoid receptor 1, a G-protein coupled receptor encoded by the GPR170 gene.

Ligand binding and activation The oxoeicosanoid receptor 1 is the receptor for a group of arachidonic acid metabolites produced by 5-lipoxygenase, such as 5-Hydroxyicosatetraenoic acid (5-HETE), 5-oxoicosanoic acid (5-oxo-ETE), and other members of this family, which are potent bioactive cell stimuli. In contrast, the GPR31 receptor binds to a different arachidonic acid metabolite, 12-hydroxyeicosatetraenoic acid (12-HETE), synthesized by 12-lipoxygenase. This conclusion is supported by studies that cloned the receptor from the PC-3 prostate cancer cell line. The cloned receptor, when expressed in other cell types, bound 12-HETE with high affinity (Kd = 5 nM) and mediated the effects of low concentrations of the S but not R stereoisomer of 12-HETE. In a [35S]GTPγS binding assay, which estimates a receptor's binding affinity by measuring its stimulation of [35S]GTPγS binding, 12(S)-HETE activated GPR31 with an EC50 (effective concentration causing a 50% of maximal [35S]GTPγS binding) of less than 0.3 nM. In comparison, the EC50 was 42 nM for 15(S)-HETE, 390 nM for 5(S)-HETE, and undetectable for 12(R)-HETE. It is currently unknown whether GPR31 interacts with structural analogs of 12(S)-HETE, such as 12-oxo-ETE (a metabolite of 12(S)-HETE), various 5,12-diHETEs including LTB4, or other bioactive metabolites like the hepoxilins. Further research is required to determine whether GPR31 exclusively binds and mediates the effects of 12(S)-HETE or, like the oxoeicosanoid receptor 1, interacts with a broader family of analogs.

Signaling pathways Like the oxoeicosanoid receptor, GPR31 activates the MEK-ERK1/2 signaling pathway, but unlike oxoeicosanoid receptor 1, it does not cause an increase in cytosolic Ca2+ concentration. It also activates NFκB. GPR31 exhibits stereospecificity and other properties expected of a true G-protein coupled receptor (GPCR).

Additional receptors activated by 12(S)-HETE 12(S)-HETE also: a) binds to and activates the leukotriene B4 receptor-2 (BLT2), a GPCR for the 5-lipoxygenase-derived metabolite LTB4; b) binds to, but inhibits, the GPCR for prostaglandin H2 and thromboxane A2, two arachidonic acid metabolites; c) binds with high affinity to a 50 kilodalton (kDa) subunit of a 650 kDa cytosolic and nuclear protein complex; and d) binds with low affinity to and activates intracellular peroxisome proliferator-activated receptor gamma.

Complications in determining GPR31 function These alternate binding sites complicate the determination of 12(S)-HETE's reliance on GPR31 for cell activation and the overall function of GPR31. Studies utilizing GPR31 Gene knockout models will be crucial for understanding its role in vivo.

Tissue distribution GPR31 receptor mRNA is highly expressed in the PC-3 prostate cancer cell line and to a lesser extent the DU145 prostate cancer cell line and to human umbilical vein endothelial cells (HUVEC), human umbilical vein endothelial cells (HUVEC), human brain microvascular endothelial cells (HBMEC), and human pulmonary aortic endothelial cells (HPAC). Its mRNA is also express but at rather low levels in several other human cell lines including: K562 cells (human myelogenous leukemia cells); Jurkat cells (T lymphocyte cells); Hut78 cells (T cell lymphoma cells), HEK 293 cells (primary embryonic kidney cells), MCF-7 cells (mammary adenocarcinoma cellss), and EJ cells (bladder carcinoma cells). Mice express an ortholog to human GPR31 in their circulating blood platelets.

Clinical significance

Prostate cancer The GPR31 receptor appears to mediate the responses of PC-3 prostate cancer cells to 12(S)-HETE in stimulating the MEK-ERK1/2 and NFκB pathways and therefore may contribute to the growth-promoting and metastasis-promoting actions that 12(S)-HETE is proposed to have in human prostate cancer. However, LNCaP and PC3 human prostate cancer cells also express BLT2 receptors; in LNCaP cells, BLT2 receptors stimulate the expression of the growth- and metastasis-promoting androgen receptor; in PC3 cells, BLT2 receptors stimulate the NF-κB pathway to inhibit the apoptosis induced by cell detachment from surfaces (i.e. Anoikis; and, in BLT2-overexpressing PWR-1E non-malignant prostate cells, 12(S)-HETE diminished anoikis-associated apoptotic cell death. Thus, the roles of 12(S)-HETE in human prostate cancer, if any, may involve its activation of either or both GPR31 and BLT2 receptors.

Other diseases The many other actions of 12(S)-HETE (see 12-Hydroxyeicosatetraenoic acid) and any other ligands found to interact with this receptor will require studies similar those conducted on PC3 cells and mesenteric arteries to determine the extent to which they interact with BLT2, TXA2/PGH2, and PPARgamma receptors and thereby may contribute in part or whole to their activity. Clues implicating the GPR31, as opposed to the other receptors in the actions of 12(S)-HETE include findings that GPR31 receptors do not respond to 12(R)-HETE nor induce rises in cytosolic Ca2+ whereas the other receptors mediate one or both of these actions. These studies will be important because, in addition to prostate cancer, preliminary studies suggest that the GPR31 receptor is implicated in several other diseases such as malignant megakaryocytis (Acute megakaryoblastic leukemia), arthritis, Alzheimer's disease, progressive B-cell chronic lymphocytic leukemia, Diabetic neuropathy, and high grade astrocytoma.

References

Illustrations

Worked examples

Example 1 — a first encounter with GPR31

Start with the simplest possible case. Write down what GPR31 claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to GPR31 before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about GPR31 ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of GPR31

In research: GPR31 appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses GPR31 in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: GPR31 is common in secondary-school and first-year university syllabi. It links to neighbouring topics G protein-coupled receptors, Genes on human chromosome 6, so understanding it makes those chapters shorter.
In everyday life: Look for GPR31 outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study GPR31 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what GPR31 means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain GPR31 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is GPR31 in simple terms?

G-protein coupled receptor 31 also known as 12-(S)-HETE receptor is a protein that in humans is encoded by the GPR31 gene. The human gene is located on chromosome 6q27 and encodes a G-protein coupled receptor protein composed of 319 amino acids.

Why does GPR31 matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study GPR31?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on GPR31.