Receptor-independent activation

Sato, M., Cismowski, M. J., Toyota, E., et al. (2006) Identification of a receptor-independent activator of G protein signaling (AGS8) in ischemic heart and its interaction with Gbetagamma. Proc. Natl. Acad. Sci. U. S. A. 103, 797-802. 

Fig. 2 Yeast-based functional screen for receptor-independent activators of G-protein signaling. The yeast strain indicated in A was generated as described previously (Cismowski et al. 1999, 2002) and transformed with mammalian cDNA libraries in the galactose-inducible yeast expression vector pYES2. The strategy for identifying mammalian cDNAs that promoted growth (i.e., activated G-protein signaling pathway) is indicated in B. GALlp GALl promoter)...

Takesono A, Cismowski Ml, Ribas C, Bernard M, Chung P, Hazard 111 S, Duzic E, Lanier SM (1999) Receptor-independent activators of heterotrimeric G-protein signaling pathways. J Biol Chem 274 33202-33205... 

Blumer JB, Smrcka AV, Lanier SM (2007) Mechanistic pathways and biological roles for receptor-independent activators of G-protein signaling. Pharmacol Ther 113 488-506... 

Davada, R. K., Chandler, L. J., and Guzman, N. J. (1994). Protein kinase C modulates receptor-independent activation of endothelial nitric oxide synthase. Eur. J. Pharmacol. 

The ability of receptors to couple to G-proteins and initiate GTPase activity may also be independent of ligand. Thus, specific mutations in a- and P-adrenergic receptors have led to receptors that mediate agonist-independent activation of adenylyl cyclase (69,70). These mutations presumably mimic the conformational state of the ligand-activated receptor when they are activated conventionally by ligands. 

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]. 

The measurement of ER has become a standard assay in the clinical management of breast cancer. The presence of ERa identifies those breast cancer patients with a lower risk of relapse and better clinical outcome. Receptor status also provides a guideline for those tumors that may be responsive to hormonal intervention. But only about half of ER-positive patients respond to hormonal therapies. Of those who respond initially, most will eventually develop an estrogen unresponsive disease following a period of treatment even though ERa is often still present. Mutant receptors and constitutively active r eceptors as well as hormone-independent activation of the ERa are discussed. The involvement of ER 3 isoforms is under investigation. 

Secondly, treatment of neutrophils with pertussis toxin, which ADP-ribosylates a neutrophil G protein and causes a loss of cell responsiveness via receptor-mediated pathways (40,41), has minimal effect on the response to HCH (Figure 11, lower panel). Thus it can be concluded that HCH activation of neutrophils is independent of receptor-mediated activation of G proteins. 

Wang J, Zhang X, Thomas SM, et al. Chemokine receptor 7 activates phosphoinositide-3-kinase-mediated invasive and prosurvival pathways in head and neck cancer cells independent of EGER. Oncogene 2005 24 5897-5904. 

A second type of NMDA-receptor-independent LTP exists in the mossy-fiber pathway at the dentate granule cell-to-CA3 pyramidal cell synapse [19]. This form of LTP, termed mossy fiber-CA3 LTP, is believed to involve PKA activation in the presynaptic cell which leads to increased neurotransmitter release. However, the exact induction mechanism is not yet clear. 

Kiss Z (1994) Tamoxifen stimulates phospholipase D activity by an estrogen receptor-independent mechanism. FEBS Lett 355 173-177... 

Ango, F., Prezeau, L., Muller, T., et al. (2001) Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer. Nature 411,962-965. 

Activation of neutrophils with PAF occurs through a G-protein-linked receptor, and the subsequent transmembrane signalling involves the stimulation of inositol phosphate metabolism. Within 30 s of addition of PAF (0.01-100 nM), intracellular Ca2+ levels increase and Ca2+ transport from the external medium is enhanced. It seems that phospholipase C-dependent and -independent activation pathways are involved in Ca2+ mobilisation. This indirectly suggests that two receptors may be involved in PAF activation. The first of these is pertussis-toxin-insensitive and may be linked to a... 

Ligand-Independent Activation of Steroid Hormone Receptors and Non-genomic Effects of Steroids... 

Bueb JL, Mousli M, Bronner C, Rouot B, Landry Y (1990) Activation of Gi-Uke proteins, a receptor-independent effect of kinins in mast cells. Mol Pharmacol 38 816—822 Burde R, Dippel E, Seifert R (1996) Receptor-independent G protein activation may account for the stimulatory effects of first-generation Hl-receptor antagonists in HL-60 cells, basophils, and mast cells. Biochem Pharmacol 51 125—131... 

Hess HA, Roper JC, Grill SW, Koelle MR (2004) RGS-7 completes a receptor-independent heterotrimeric G protein cycle to asymmetrically regulate mitotic spindle positioning in C. elegans. Cell 119 209-218 Higashijima T, Burnier J, Ross EM (1990) Regulation of Gi and Go by mastoparan, related amphiphilic peptides, and hydrophobic amines mechanism and structural determinants of activity. J Biol Chem 265 14176-14186... 

Klinker IF, Seifert R (1997) Morphine and muscle relaxants are receptor-independent G-protein activators and cromolyn is an inhibitor of stimulated G-protein activity. Inflamm Res 46 46—50 Klinker IF, Seifert R, Datum H, Rommelspacher H (1997) Activation by beta-carbohnes of G-proteins in HL-60 membranes and the bovine retinal G-protein transducin in a receptor-independent manner. Biochem Pharmacol 53 1621-1626... 

Power, R.F., Maui, S.K., Codina, J., Conneely, O.M.and O Malley, B.W. Dopaminergic and Ligand-independent activation of steroid hormone receptors (1991) Science 254,1636-1639... 

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