Editing G protein-coupled receptor (section)

====Examples====

In the late 1990s, evidence began accumulating to suggest that some GPCRs are able to signal without G proteins. The [[MAPK1|ERK2]] mitogen-activated protein kinase, a key signal transduction mediator downstream of receptor activation in many pathways, has been shown to be activated in response to cAMP-mediated receptor activation in the [[slime mold]] [[Dictyostelium discoideum|''D. discoideum'']] despite the absence of the associated G protein α- and β-subunits.<ref>{{cite journal | vauthors = Kim JY, Haastert PV, Devreotes PN | title = Social senses: G-protein-coupled receptor signaling pathways in Dictyostelium discoideum | journal = Chemistry & Biology | volume = 3 | issue = 4 | pages = 239–43 | date = April 1996 | pmid = 8807851 | doi = 10.1016/S1074-5521(96)90103-9 | doi-access = free }}</ref>

In mammalian cells, the much-studied β<sub>2</sub>-adrenoceptor has been demonstrated to activate the ERK2 pathway after arrestin-mediated uncoupling of G-protein-mediated signaling. Therefore, it seems likely that some mechanisms previously believed related purely to receptor desensitisation are actually examples of receptors switching their signaling pathway, rather than simply being switched off.

In kidney cells, the [[bradykinin receptor B2]] has been shown to interact directly with a protein tyrosine phosphatase. The presence of a tyrosine-phosphorylated [[immunoreceptor tyrosine-based inhibitory motif|ITIM]] (immunoreceptor tyrosine-based inhibitory motif) sequence in the B2 receptor is necessary to mediate this interaction and subsequently the antiproliferative effect of bradykinin.<ref>{{cite journal | vauthors = Duchene J, Schanstra JP, Pecher C, Pizard A, Susini C, Esteve JP, Bascands JL, Girolami JP | title = A novel protein-protein interaction between a G protein-coupled receptor and the phosphatase SHP-2 is involved in bradykinin-induced inhibition of cell proliferation | journal = The Journal of Biological Chemistry | volume = 277 | issue = 43 | pages = 40375–83 | date = October 2002 | pmid = 12177051 | doi = 10.1074/jbc.M202744200 | doi-access = free }}</ref>