Rhodopsin-family receptors associate with small G proteins to activate phospholipase D

Mitchell, Rory; McCulloch, Derek; Lutz, Eve M.; Johnson, Mark; MacKenzie, Cameron A.; Fennell, Myles; Fink, George; Zhou, Wei; Sealfon, Stuart C.

doi:10.1038/32937

Cited by 205 publications

(190 citation statements)

References 26 publications

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“…There are many examples of association of the GPCRs, including MOP with other proteins, such as beta-arrestins, (Lefkowitz, 1998), GRKs (Pitcher et al, 1998) and small G proteins (Mitchell et al, 1998). Different laboratories, including ours, have reported interaction of MOP C-tail with different proteins, such as periplakin (Feng et al, 2003), Phospholipase D2 (Koch et al, 2003), mPKCI (Guang et al, 2004), HSP40 {Ancevska-Taneva, 2006 #5292)and Filamin A (Onoprishvili et al, 2003).…”

Section: Introductionmentioning

confidence: 85%

Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

Onoprishvili

Simon

2007

Brain Research

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We investigated the effects of morphine and other agonists on the human mu opioid receptor (MOP) expressed in M2 melanoma cells, lacking the actin cytoskeleton protein filamin A and in A7, a sub clone of the M2 melanoma cells, stably transfected with filamin A cDNA. The results of binding experiments showed, that after chronic morphine treatment (24 hr) of A7 cells, MOP binding sites were down-regulated to 63% of control, whereas, unexpectedly, in M2 cells, MOP binding was upregulated to 188% of control naïve cells. Similar up-regulation was observed with the agonists methadone and levorphanol. The presence of antagonists (naloxone or CTAP) during chronic morphine treatment inhibited MOP down-regulation in A7 cells. In contrast, morphine-induced upregulation of MOP in M2 cells was further increased by these antagonists. Chronic morphine desensitized MOP in A7 cells, i.e. it decreased DAMGO-induced stimulation of GTPγS binding. In M2 cells DAMGO stimulation of GTPγS binding was significantly greater than in A7 cells and was not desensitized by chronic morphine. Pertussis toxin treatment abolished morphine-induced receptor up-regulation in M2 cells, whereas it had no effect on morphine-induced down-regulation in A7 cells. These results indicate that, in the absence of filamin A, chronic treatment with morphine, methadone or levorphanol leads to up-regulation of MOP, to our knowledge, the first instance of opioid receptor up-regulation by agonists in cell culture.

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Section: Introductionmentioning

confidence: 85%

Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

Onoprishvili

Simon

2007

Brain Research

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“…Subsequently, the crystal structure of bovine rhodopsin revealed that these residues are capable of interacting through a water molecule [110] thus validating the GnRH receptor models. Interestingly, this exchange prevents the human GnRH receptor coupling to phospholipase D by the small G-proteins ARF and RhoA, implying receptor conformationdependent signaling selectivity [98].…”

Section: Gnrh Receptor Structure and Functionmentioning

confidence: 99%

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

Millar

Pawson

Morgan

et al. 2008

Frontiers in Neuroendocrinology

122

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Geoffrey Wingfield Harris' demonstration of hypothalamic hormones regulating pituitary function led to their structural identification and therapeutic utilization in a wide spectrum of diseases. Amongst these, Gonadotropin Releasing Hormone (GnRH) and its analogs are widely employed in modulating gonadotropin and sex steroid secretion to treat infertility, precocious puberty and many hormone-dependent diseases including endometriosis, uterine fibroids and prostatic cancer. While these effects are all mediated via modulation of the pituitary gonadotrope GnRH receptor and the G q signaling pathway, it has become increasingly apparent that GnRH regulates many extrapituitary cells in the nervous system and periphery. This review focuses on two such examples, namely GnRH analog effects on reproductive behaviors and GnRH analog effects on the inhibition of cancer cell growth. For both effects the relative activities of a range of GnRH analogs is distinctly different from their effects on the pituitary gonadotrope and different signaling pathways are utilized. As there is only a single functional GnRH receptor type in man we have proposed that the GnRH receptor can assume different conformations which have different selectivity for GnRH analogs and intracellular signaling proteins complexes. This ligand-induced selective-signaling recruits certain pathways while by-passing others and has implications in developing more selective GnRH analogs for highly specific therapeutic intervention.

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“…The substitution of the Asn residue in the NPXXY motif in different GPCRs has been shown to affect the activation of adenylyl cyclase [19], phospholipase C [20], [21], phospholipase D [22], and internalization pathways [23 -24].…”

Section: Homology Of Fatty Acid Binding Receptors To Class a Gpcrs Amentioning

confidence: 99%

Fatty Acid Binding Receptors and Their Physiological Role in Type 2 Diabetes

Swaminath

2008

Archiv der Pharmazie

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G‐protein‐coupled receptors (GPCRs) respond to various physiological ligands such as photons, ions, and small molecules that include amines, fatty acids, and amino acids to peptides, proteins and steroids. Therefore, this family of proteins represents an attractive target for biopharmaceutical research [1]. The physiological role of fatty acids and other lipid molecules as important signal mediators is well studied in various metabolic pathways [2]. Acute administration of free fatty acids (FFAs) stimulates insulin release. Conversely, chronic exposure to high levels of free fatty acids leads to impairment of β cell function and lipotoxicity. However, the receptors through which these fatty acids and lipids act were unknown, until the identification of fatty acid binding receptors: GPR40, GPR41, GPR43, and GPR119. Based on their tissue‐expression profile, and pharmacologic analysis, the fatty acid binding receptors along with lipid binding receptor GPR119 are linked to diabetes and obesity. They play a critical role in the metabolic regulation of insulin release and glucose homeostasis. In this review, the mechanism of receptor activation, pharmacology, and the physiological functions of the fatty acid binding receptors will be discussed.

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Rhodopsin-family receptors associate with small G proteins to activate phospholipase D

Cited by 205 publications

References 26 publications

Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

Fatty Acid Binding Receptors and Their Physiological Role in Type 2 Diabetes

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