PAQR Proteins: A Novel Membrane Receptor Family Defined by an Ancient7-Transmembrane Pass Motif

Tang, Yongkai; Hu, Tianhua; Arterburn, Matthew; Boyle, Bryan; Bright, Jessica M.; Emtage, Peter; Funk, Walter D.

doi:10.1007/s00239-004-0375-2

Cited by 324 publications

(275 citation statements)

References 18 publications

Supporting

Mentioning

261

Contrasting

Unclassified

Order By: Relevance

“…Adiponectin receptors belong to a new seven-transmembrane receptor family termed PAQR; these receptors have the N-terminus facing the cytosol, unlike GPCRs [3,20]. In previous experiments, we found that, when overexpressed in Hela cells, AdipoR1 is distributed in the cytoplasm with a punctate pattern and AdipoR2 is dispersed in the cytosol without obvious puncta (data not shown), indicating that AdipoR1 could be localized both in the plasma membrane and in the cytosol.…”

Section: Endocytosis Of Adipor1mentioning

confidence: 80%

“…To analyze only the plasma membranelocalized receptors, we generated C-terminally Myc-tagged AdipoR1 and AdipoR2 and used them to analyze endocytosis in HEK293T cells, a cell line commonly used to observe receptor endocytosis. The C-termini of adiponectin receptors are proposed to localize to the extracellular side of the plasma membrane [3,20]. The tagged receptors on the cell surface were labeled at 4 ºC with an anti-Myc antibody and a fluorescently conjugated secondary antibody.…”

Section: Endocytosis Of Adipor1mentioning

confidence: 99%

See 1 more Smart Citation

Endocytosis of adiponectin receptor 1 through a clathrin- and Rab5-dependent pathway

2008

View full text Add to dashboard Cite

In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical roles in the pathogenesis of diabetes and metabolic syndrome. Here, we analyzed the endocytosis of adiponectin and adiponectin receptor 1 (AdipoR1) and found that they are both internalized into transferrin-positive compartments that follow similar traffic routes. Blocking clathrin-mediated endocytosis by expressing Eps15 mutants or depleting K + trapped AdipoR1 at the plasma membrane, and K + depletion abolished adiponectin internalization, indicating that the endocytosis of AdipoR1 and adiponectin is clathrin-dependent. Depletion of K + and overexpression of Eps15 mutants enhance adiponectinstimulated AMP-activated protein kinase phosphorylation, suggesting that the endocytosis of AdipoR1 might downregulate adiponectin signaling. In addition, AdipoR1 colocalizes with the small GTPase Rab5, and a dominant negative Rab5 abrogates AdipoR1 endocytosis. These data indicate that AdipoR1 is internalized through a clathrin-and Rab5-dependent pathway and that endocytosis may play a role in the regulation of adiponectin signaling.

show abstract

Section: Endocytosis Of Adipor1mentioning

confidence: 80%

Section: Endocytosis Of Adipor1mentioning

confidence: 99%

Endocytosis of adiponectin receptor 1 through a clathrin- and Rab5-dependent pathway

2008

View full text Add to dashboard Cite

show abstract

“…Adiponectin plays an important role in the regulation of energy and glucose metabolism (21). RKTG was originally named PAQR3 (progestin and adipoQ receptor 3) with uncharacterized function (22). The human RKTG protein contains 311 amino acid residues (Fig.…”

Section: Resultsmentioning

confidence: 99%

Spatial regulation of Raf kinase signaling by RKTG

Lin

Xie

Ding

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

116

137

View full text Add to dashboard Cite

Subcellular compartmentalization has become an important theme in cell signaling such as spatial regulation of Ras by RasGRP1 and MEK/ERK by Sef. Here, we report spatial regulation of Raf kinase by RKTG (Raf kinase trapping to Golgi). RKTG is a seven-transmembrane protein localized at the Golgi apparatus. RKTG expression inhibits EGF-stimulated ERK and RSK phosphorylation, blocks NGF-mediated PC12 cell differentiation, and antagonizes Ras-and Raf-1-stimulated Elk-1 transactivation. Through interaction with Raf-1, RKTG changes the localization of Raf-1 from cytoplasm to the Golgi apparatus, blocks EGF-stimulated Raf-1 membrane translocation, and reduces the interaction of Raf-1 with Ras and MEK1. In RKTG-null mice, the basal ERK phosphorylation level is increased in the brain and liver. In RKTG-deleted mouse embryonic fibroblasts, EGF-induced ERK phosphorylation is enhanced. Collectively, our results reveal a paradigm of spatial regulation of Raf kinase by RKTG via sequestrating Raf-1 to the Golgi apparatus and thereby inhibiting the ERK signaling pathway.R af kinase relays the signals from Ras to MEK (MAPK and ERK kinase) and ERK/MAPK (1, 2). This pathway regulates many fundamental cellular functions, including cell proliferation, apoptosis, differentiation, motility, and metabolism, and is implicated in many human diseases including cancer (3). In the Ras/Raf/MEK/ ERK signaling cascade, several players within this pathway are exquisitely regulated by subcellular compartmentalization (4, 5). Kinase suppressor of Ras (KSR) is a scaffold protein that coordinates the assembly of multiprotein MAPK complex in plasma membrane (6). ␤-Arrestin could also function as a scaffold protein to target the MAPK protein complex to early endosome (7). Different lipid anchors are able to shuttle Ras between different membrane compartments to modulate subcellular Ras signaling (8-10). In T lymphocyte, Ras could be activated in situ on the Golgi apparatus via the Ras exchange factor RasGRP1, which is activated by phospholipase C (11). Compartmentalized signaling of Ras/ MAPK in T lymphocyte on either plasma membrane or Golgi apparatus leads to distinct output of ERK activation and thereby determines the threshold of thymic selection (12). MEK could be targeted to endosome by a scaffold protein MP1 through adaptor p14 (13). It was also found that MEK/ERK can be recruited to the Golgi by Sef, and that such spatial regulation blocks the Ras signaling to the nucleus but not to the cytosol (14). However, how Raf is regulated in a spatial manner has not been characterized.The activity of Raf kinase is mainly regulated by phosphorylation events and scaffold proteins (1, 2). In addition, Raf could be negatively regulated by interaction with other proteins. Raf kinase inhibitor protein (RKIP) is able to interact with Raf-1, MEK, and ERK (15). RKIP blocks Raf-1 signaling to MEK by competitively disrupting the interaction between Raf-1 and MEK because both Raf-1 and MEK bind to overlapping sites in RKIP (15, 16). After stimulation of G protein...

show abstract

“…Overexpressing these receptors in mammalian cells did not lead to enhanced binding of recombinant CTRP1, suggesting that CTRP1 binds to its own unique receptor. 6 AdipoR1 and AdipoR2 belong to the progestin and adipoQ receptor (PAQR) family of conserved seventransmembrane proteins currently comprising 11 members encoded by distinct genes in humans (55). It remains to be determined whether any of the PAQR family members can serve as receptor for CTRP1.…”

Section: Discussionmentioning

confidence: 99%

CTRP1 Protein Enhances Fatty Acid Oxidation via AMP-activated Protein Kinase (AMPK) Activation and Acetyl-CoA Carboxylase (ACC) Inhibition

Peterson

Aja

Wei

et al. 2012

Journal of Biological Chemistry

142

108

View full text Add to dashboard Cite

show abstract

PAQR Proteins: A Novel Membrane Receptor Family Defined by an Ancient7-Transmembrane Pass Motif

Cited by 324 publications

References 18 publications

Endocytosis of adiponectin receptor 1 through a clathrin- and Rab5-dependent pathway

Endocytosis of adiponectin receptor 1 through a clathrin- and Rab5-dependent pathway

Spatial regulation of Raf kinase signaling by RKTG

CTRP1 Protein Enhances Fatty Acid Oxidation via AMP-activated Protein Kinase (AMPK) Activation and Acetyl-CoA Carboxylase (ACC) Inhibition

Contact Info

Product

Resources

About