G-protein-independent signaling

Heuss, C., Scanziani, M., Gahwiler, B. H., and Gerber, U. (1999) G protein-independent signaling mediated by metabotropic glutamate receptors. Nat. Neurosci. 2,1070-1077. 

Steen, A., Larsen, O., Thiele, S., Rosenkilde, M. M. (2014). Biased and G protein-independent signaling of chemokine receptors. Frontiers in Immunology, 5, 211. 

Signaling via 7TM receptors can occur through several different pathways (Marinissen Gutkind, 2001) and is most often described as G protein dependent or G protein independent. The former includes signaling through the Ga or Gpy subunits of G proteins, while the latter includes s -naling induced by P-arrestin recruitment, among others. 

Finally, the atypical chemokine receptors ACKRl—6 (Bachelerie et al., 2014) are able to recruit chemokines and signal via P-arrestin-dependent pathways, but do not couple to G proteins (Graham, Locati, Mantovani, Rot, Thelen, 2012). Thus, scavenger or atypical receptors are firUy biased toward G protein-independent pathways. 

Apelin receptors activate several signalling pathways including coupling through inhibitory G-proteins (G ) and Ras-independent activation of extracellular-regulated kinases (ERKs) via protein kinase C (PKC). The apelin receptor is one of number of G-protein-coupled receptors that can act as an alternative coreceptor for entry into cells of HIV and simian immunodeficiency vims (SIV) strains in human U87 cells expressing CD4 in vitro. Apelin peptides blocks entry of HIV but display different potencies, with apelin-36 being more effective than shorter sequences [3]. 

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