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Receptors & Clinical Investigation

Sébastien S Dufresne, Antoine Boulanger-Piette, Sabrina Bossé, Jérôme Frenette
The bone remodeling and homeostasis are mainly controlled by the receptor-activator of nuclear factor kB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin (OPG) pathway. While there is a strong association between osteoporosis and skeletal muscle dysfunction, the functional relevance of a particular biological pathway that synchronously regulates bone and skeletal muscle physiopathology remains elusive. Our recent article published in the American Journal of Physiology (Cell Physiology) showed that RANK is also expressed in fully differentiated C2C12 myotubes and skeletal muscles...
May 30, 2016: Receptors & Clinical Investigation
Lucia Mendoza-Viveros, Arthur H Cheng, Hai-Ying M Cheng
G protein-coupled receptor kinases (GRKs) are a family of serine/threonine protein kinases that terminate G protein-coupled receptor (GPCR) signaling by phosphorylating the receptor and inducing its internalization. In addition to their canonical function, some GRKs can phosphorylate non-GPCR substrates and regulate GPCR signaling in a kinase-independent manner. GPCRs are abundantly expressed in the suprachiasmatic nucleus (SCN), a structure in the mammalian brain that serves as the central circadian pacemaker...
February 1, 2016: Receptors & Clinical Investigation
Andrew J Bryant, Edward W Scott
Pulmonary hypertension complicating idiopathic pulmonary fibrosis, also known as secondary pulmonary hypertension, represents a major source of morbidity and mortality in affected patients. While the study of primary pulmonary arterial hypertension has yielded several therapies, the same is not true for the treatment of pulmonary hypertension secondary to pulmonary fibrosis. Recent studies have indicated an important role of hypoxia-inducible factor (HIF) - a regulatory protein that is vital in adaptation to hypoxic conditions - in the development of secondary pulmonary hypertension...
2016: Receptors & Clinical Investigation
Nataliia V Shults, Dividutta Das, Yuichiro J Suzuki
Major vault protein (MVP) is the major component of the vault particle whose functions are not well understood. One proposed function of the vault is to serve as a mechanism of drug transport, which confers drug resistance in cancer cells. We show that MVP can be found in cardiac and smooth muscle. In human airway smooth muscle cells, knocking down MVP was found to cause cell death, suggesting that MVP serves as a cell survival factor. Further, our laboratory found that MVP is S-glutathionylated in response to ligand/receptor-mediated cell signaling...
2016: Receptors & Clinical Investigation
Katherine Upchurch, SangKon Oh, HyeMee Joo
Dendritic cells (DCs) are major antigen-presenting cells (APCs) that can induce and control host immune responses. DCs express pattern recognition receptors (PRRs), which can translate external and internal triggers into different types of T cell responses. The types of CD4(+) T cell responses elicited by DCs (e.g., Th1, Th2, Th17, Th21, Th22 and regulatory T cells (Tregs)) are associated with either host immunity or inflammatory diseases, including allergic diseases and autoimmune diseases. In particular, the pathogenic functions of Th2-type T cells in allergic immune disorders have been well documented, although Th2-type T cell responses are crucial for immunity against certain parasite infections...
January 1, 2016: Receptors & Clinical Investigation
Jenna Ciesielski, Tsung-Ping Su, Shang-Yi Tsai
Neurodegenerative diseases are linked to tauopathy as a result of cyclin dependent kinase 5 (cdk5) binding to its p25 activator instead of its p35 activator and becoming over-activated. The overactive complex stimulates the hyperphosphorylation of tau proteins, leading to neurofibrillary tangles (NFTs) and stunting axon growth and development. It is known that the sigma-1 receptor (Sig-1R), an endoplasmic reticulum chaperone, can be involved in axon growth by promoting neurite sprouting through nerve growth factor (NGF) and tropomyosin receptor kinase B (TrkB)([1, 2])...
2016: Receptors & Clinical Investigation
Kai Yang, Qian Jiang, Ziyi Wang, Meichan Li, Qian Zhang, Wenju Lu, Jian Wang
Transcription factor hypoxia-inducible factor 1α (Hif-1α) is known for its crucial role in promoting the pathogenesis of pulmonary hypertension (PH). Previous studies have indicated the in-depth mechanisms that Hif-1α increases the distal pulmonary arterial (PA) pressure and vascular remodeling by triggering the intracellular calcium homeostasis, especially the store-operated calcium entry (SOCE) process. In our recent research paper published in the Journal of Molecular Medicine, we found that the transcription factor peroxisome proliferator-activated receptor γ (PPARγ) activation could attenuate the PH pathogenesis by suppressing the elevated distal PA pressure and vascular remodeling...
2015: Receptors & Clinical Investigation
Ivan H Chan, Victoria Wu, Scott McCauley, Elizabeth A Grimm, John B Mumm
Recent advances in immunoncology have dramatically changed the treatment options available to cancer patients. However, the fundamental challenges with this therapeutic modality are not new and still persist with the current wave of immunoncology compounds. These challenges are centered on the activation and expansion, induction of intratumoral infiltration and persistence of highly activated, cytotoxic, tumor antigen specific CD8+ T cells. We have investigated the anti-tumor mechanism of action of pegylated recombinant interleukin-10, (PEG-rIL-10) both pre-clinically with murine (PEG-rMuIL-10) and now clinically (AM0010) with human pegylated interleukin-10...
2015: Receptors & Clinical Investigation
Nance Yuan, Kameron S Rezzadeh, Justine C Lee
Skeletal regenerative medicine emerged as a field of investigation to address large osseous deficiencies secondary to congenital, traumatic, and post-oncologic conditions. Although autologous bone grafts have been the gold standard for reconstruction of skeletal defects, donor site morbidity remains a significant limitation. To address these limitations, contemporary bone tissue engineering research aims to target delivery of osteogenic cells and growth factors in a defined three dimensional space using scaffolding material...
2015: Receptors & Clinical Investigation
Sandeep Artham, Abdelrahman Y Fouda, Azza B El-Remessy, Susan C Fagan
No abstract text is available yet for this article.
2015: Receptors & Clinical Investigation
Yeon Sun Lee, Sara M Hall, Cyf Ramos-Colon, Michael Remesic, David Rankin, Todd W Vanderah, Frank Porreca, Josephine Lai, Victor J Hruby
Dynorphin A (Dyn A) is an endogenous opioid ligand that possesses neuroinhibitory (antinociceptive) effects via μ, δ, and κ opioid receptors. However, under chronic pain conditions, up-regulated spinal Dyn A can also interact with bradykinin receptors (BRs) to promote hyperalgesia through a neuroexcitatory(pronociceptive) effect. These excitatory effects cannot be blocked by an opioid antagonist, and thus are non-opioid in nature. On the basis of the structural dissimilarity between Dyn A and endogenous BR ligands, bradykinin(BK) and kallidin (KD), Dyn A's interaction with BRs could not be predicted, and provided an opportunity to identify a novel potential neuroexcitatory target...
2015: Receptors & Clinical Investigation
Jonathan H Shannahan, Wei Bai, Jared M Brown
Nanomaterials (NMs) are being utilized in a variety of biomedical applications including drug delivery, diagnostics, and therapeutic targeting. These applications are made possible due to the unique physicochemical properties that are exhibited at the nanoscale. To ensure safe development of NMs for clinical use, it is necessary to understand their interactions with cells and specifically cell surface receptors, which will facilitate either their toxicity and/or clinical function. Recently our research and others have investigated the role of scavenger receptors in mediating NM-cell interactions and responses...
2015: Receptors & Clinical Investigation
Kazunori Hamamura, Andy Chen, Hiroki Yokota
The phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) is activated in response to various stresses such as viral infection, nutrient deprivation, and stress to the endoplasmic reticulum. Severe stress to the endoplasmic reticulum, for instance, induces an apoptotic pathway, while mild stress, on the contrary, leads to a pro-survival pathway. Little has been known about the elaborate role of eIF2α phosphorylation in the development of bone-forming osteoblasts and bone-resorbing osteoclasts...
2015: Receptors & Clinical Investigation
Sue-Chin Lee, Yuko Fujiwara, Gabor J Tigyi
The role of the lysophospholipase D autotaxin (ATX) and lysophosphatidic acid (LPA) in cancer is emerging and represents two key players in regulating cancer progression. In this brief review, we will discuss some of our recent findings, which highlight a central role that LPA and its receptor plays in orchestrating melanoma-stroma interactions in the establishment of lung metastases. In particular, we evaluated not only the function of LPA receptors on tumor cells but also their role on host tissues and how they can influence melanoma growth and metastasis...
2015: Receptors & Clinical Investigation
Andrew J Payne, Simon Kaja, Peter Koulen
No abstract text is available yet for this article.
2015: Receptors & Clinical Investigation
Eric Erbs, Lauren Faget, Pierre Veinante, Brigitte L Kieffer, Dominique Massotte
Opioid receptors belong to the G protein coupled receptor family. They modulate brain function at all levels of neural integration and therefore impact on autonomous, sensory, emotional and cognitive processing. In vivo functional interaction between mu and delta opioid receptors are known to take place though it is still debated whether interactions occur at circuitry, cellular or molecular level. Also, the notion of receptor crosstalk via mu-delta heteromers is well documented in vitro but in vivo evidence remains scarce...
September 2014: Receptors & Clinical Investigation
Chinmoy Patra, Kelly R Monk, Felix B Engel
The G protein-coupled receptor (GPCR) superfamily is the largest known receptor family in the human genome. Although the family of adhesion GPCRs comprises the second largest sub-family, their function is poorly understood. Here, we review the current knowledge about the adhesion GPCR family member GPR126. GPR126 possesses a signal peptide, a 7TM domain homologous to secretin-like GPCRs, a GPS motif and an extended N-terminus containing a CUB (Complement, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a hormone binding domain and 27 putative N-glycosylation sites...
July 1, 2014: Receptors & Clinical Investigation
Yoko Shiba, Paul A Randazzo
Mammalian cells have many membranous organelles that require proper composition of proteins and lipids. Cargo sorting is a process required for transporting specific proteins and lipids to appropriate organelles, and if this process is disrupted, organelle function as well as cell function is disrupted. ArfGAP family proteins have been found to be critical for receptor sorting. In this review, we summarize our recent knowledge about the mechanism of cargo sorting that require function of ArfGAPs in promoting the formation of transport vesicles, and discuss the involvement of specific ArfGAPs for the sorting of a variety of receptors, such as MPR, EGFR, TfR, Glut4, TRAIL-R1/DR4, M5-muscarinic receptor, c-KIT, rhodopsin and β1-integrin...
June 13, 2014: Receptors & Clinical Investigation
Trivendra Tripathi, Hassan Alizadeh
Protease-activated receptors (PARs) belong to a unique family of G protein-coupled receptors (GPCRs) that are cleaved at an activation site within the N-terminal exodomain by a variety of proteinases, essentially of the serine (Ser) proteinase family. After cleavage, the new N-terminal sequence functions as a tethered ligand, which binds intramolecularly to activate the receptor and initiate signaling. Cell signals induced through the activation of PARs appear to play a significant role in innate and adoptive immune responses of the cornea, which is constantly exposed to proteinases under physiological or pathophysiological conditions...
2014: Receptors & Clinical Investigation
Jie Feng, Xiaojun Xu, Bo Li, Edward Brown, Alton B Farris, Shi-Yong Sun, Jenny J Yang
The calcium-sensing receptor (CaSR) is the principal regulator of the secretion of parathyroid hormone and plays key roles in extracellular calcium (Ca(2+) o) homeostasis. It is also thought to participate in the development of cancer, especially bony metastases of breast and prostate cancer. However, the expression of CaSR has not been systematically analyzed in prostate cancer from patients with or without bony metastases. By comparing human prostate cancer tissue sections in microarrays, we found that the CaSR was expressed in both normal prostate and primary prostate cancer as assessed by immunohistochemistry (IHC)...
2014: Receptors & Clinical Investigation
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