Editing Signal transduction (section)

====G protein–coupled receptors====
{{Main|G protein–coupled receptor}}
G protein–coupled receptors (GPCRs) are a family of integral transmembrane proteins that possess seven transmembrane domains and are linked to a heterotrimeric [[G protein]]. With nearly 800 members, this is the largest family of membrane proteins and receptors in mammals. Counting all animal species, they add up to over 5000.<ref name="F2005">{{Cite journal |vauthors=Fredriksson R, Schiöth HB |date=May 2005 |title=The repertoire of G-protein-coupled receptors in fully sequenced genomes |journal=Molecular Pharmacology |volume=67 |issue=5 |pages=1414–25 |doi=10.1124/mol.104.009001 |pmid=15687224 |s2cid=7938806}}</ref> Mammalian GPCRs are classified into 5 major families: [[Rhodopsin-like receptors|rhodopsin-like]], [[Secretin receptor family|secretin-like]], [[Metabotropic glutamate receptor|metabotropic glutamate]], [[Adhesion-GPCR|adhesion]] and [[frizzled]]/[[smoothened]], with a few GPCR groups being difficult to classify due to low sequence similarity, e.g. [[vomeronasal receptor]]s.<ref name="F2005" /> Other classes exist in eukaryotes, such as the ''[[Dictyostelium]]'' [[cyclic AMP receptors]] and [[fungal mating pheromone receptors]].<ref name="F2005" />

Signal transduction by a GPCR begins with an inactive G protein coupled to the receptor; the G protein exists as a heterotrimer consisting of Gα, Gβ, and Gγ subunits.<ref name=" pmid=21873996 ">{{Cite journal |vauthors=Qin K, Dong C, Wu G, Lambert NA |date=August 2011 |title=Inactive-state preassembly of G(q)-coupled receptors and G(q) heterotrimers |journal=Nature Chemical Biology |volume=7 |issue=10 |pages=740–7 |doi=10.1038/nchembio.642 |pmc=3177959 |pmid=21873996}}</ref> Once the GPCR recognizes a ligand, the conformation of the receptor changes to activate the G protein, causing Gα to bind a molecule of GTP and dissociate from the other two G-protein subunits. The dissociation exposes sites on the subunits that can interact with other molecules.<ref>{{Cite book |last=Berg |first=Jeremy M. |url=https://archive.org/details/biochemistry200100jere |title=Biochemistry |last2=Tymoczko |first2=John L. |last3=Stryer |first3=Lubert |last4=Clarke |first4=Neil D. |publisher=W.H. Freeman |year=2002 |isbn=978-0-7167-4954-7 |location=San Francisco |name-list-style=vanc}}</ref> The activated G protein subunits detach from the receptor and initiate signaling from many downstream effector proteins such as [[phospholipase]]s and [[ion channels]], the latter permitting the release of second messenger molecules.<ref>{{Cite journal |vauthors=Yang W, Xia S |year=2006 |title=Mechanisms of regulation and function of G-protein-coupled receptor kinases |journal=World J Gastroenterol |volume=12 |issue=48 |pages=7753–7 |doi=10.3748/wjg.v12.i48.7753 |pmc=4087537 |pmid=17203515 |doi-access=free}}</ref> The total strength of signal amplification by a GPCR is determined by the lifetimes of the ligand-receptor complex and receptor-effector protein complex and the deactivation time of the activated receptor and effectors through intrinsic enzymatic activity; e.g. via protein kinase phosphorylation or b-arrestin-dependent internalization.{{cn|date=April 2025}}

A study was conducted where a [[point mutation]] was inserted into the gene encoding the [[chemokine]] receptor CXCR2; mutated cells underwent a [[malignant transformation]] due to the [[gene expression|expression]] of CXCR2 in an active conformation despite the absence of chemokine-binding. This meant that chemokine receptors can contribute to cancer development.<ref name="burger">{{Cite journal |vauthors=Burger M, Burger JA, Hoch RC, Oades Z, Takamori H, Schraufstatter IU |date=August 1999 |title=Point mutation causing constitutive signaling of CXCR2 leads to transforming activity similar to Kaposi's sarcoma herpesvirus-G protein-coupled receptor |journal=Journal of Immunology |volume=163 |issue=4 |pages=2017–22 |doi=10.4049/jimmunol.163.4.2017 |pmid=10438939 |s2cid=45743458 |doi-access=free}}</ref>