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    4576 results match your criteria Cellular Signalling [Journal]

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    Non-visual arrestins regulate the focal adhesion formation via small GTPases RhoA and Rac1 independently of GPCRs.
    Cell Signal 2017 Nov 11;42:259-269. Epub 2017 Nov 11.
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, United States. Electronic address:
    Arrestins recruit a variety of signaling proteins to active phosphorylated G protein-coupled receptors in the plasma membrane and to the cytoskeleton. Loss of arrestins leads to decreased cell migration, altered cell shape, and an increase in focal adhesions. Small GTPases of the Rho family are molecular switches that regulate actin cytoskeleton and affect a variety of dynamic cellular functions including cell migration and cell morphology. Read More

    Cln5 is secreted and functions as a glycoside hydrolase in Dictyostelium.
    Cell Signal 2017 Nov 8;42:236-248. Epub 2017 Nov 8.
    Trent University, Department of Biology, 1600 West Bank Drive, Peterborough, Ontario K9L 0G2, Canada. Electronic address:
    Ceroid lipofuscinosis neuronal 5 (CLN5) is a member of a family of proteins that are linked to neuronal ceroid lipofuscinosis (NCL). This devastating neurological disorder, known commonly as Batten disease, affects all ages and ethnicities and is currently incurable. The precise function of CLN5, like many of the NCL proteins, remains to be elucidated. Read More

    Enhancement of inosine-mediated A2AR signaling through positive allosteric modulation.
    Cell Signal 2017 Nov 8;42:227-235. Epub 2017 Nov 8.
    Molecular Medicine Research Institute, 428 Oakmead Parkway, Sunnyvale, CA 94085.
    Inosine is an endogenous nucleoside that is produced by metabolic deamination of adenosine. Inosine is metabolically more stable (half-life 15h) than adenosine (half-life <10s). Inosine exerts anti-inflammatory and immunomodulatory effects similar to those observed with adenosine. Read More

    Involvement of glucose related energy crisis and endoplasmic reticulum stress: Insinuation of streptozotocin induced Alzheimer's like pathology.
    Cell Signal 2017 Nov 7;42:211-226. Epub 2017 Nov 7.
    Academy of Scientific and Innovative Research (AcSIR), Lucknow 226031, Uttar Pradesh, India. Electronic address:
    The present study was conducted to correlate the cellular and molecular alterations in Alzheimer's pathology employing streptozotocin (STZ) induced experimental rat model. The STZ was administered in rat brain bilaterally by intracerebroventricular route using stereotaxic surgery followed by donepezil dosing. The Alzheimer's related pathological marker like acetylcholinesterase (AChE) activity, tau phosphorylation and amyloid aggregation were observed after STZ administration. Read More

    IL-13 enhances mesenchymal transition of pulmonary artery endothelial cells via down-regulation of miR-424/503 in vitro.
    Cell Signal 2017 Nov 1. Epub 2017 Nov 1.
    Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8520, Japan.
    Pulmonary arterial hypertension (PAH) has a major effect on life expectancy with functional degeneracy of the lungs and right heart. Interleukin-13 (IL-13), one of the type 2 cytokines mainly associated with allergic diseases, has recently been reported to be associated with Schistosomiasis-associated PAH which shares pathological features with other forms of PAH, such as idiopathic PAH and connective tissue disease-associated PAH. But a direct pathological role of IL-13 in the development of PAH has not been explored. Read More

    Overexpression of dJmj differentially affects intestinal stem cells and differentiated enterocytes.
    Cell Signal 2017 Nov 2;42:194-210. Epub 2017 Nov 2.
    Department of Applied Biology, The Center for Advanced Insect Research, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. Electronic address:
    Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 independent function is suggested for Drosophila Jumonji (dJmj). Read More

    Site-specific O-glycosylation of N-terminal serine residues by polypeptide GalNAc-transferase 2 modulates human δ-opioid receptor turnover at the plasma membrane.
    Cell Signal 2017 Oct 31;42:184-193. Epub 2017 Oct 31.
    Medical Research Center Oulu, Research Unit of Biomedicine, University of Oulu, FI-90014 Oulu, Finland. Electronic address:
    G protein-coupled receptors (GPCRs) are an important protein family of signalling receptors that govern a wide variety of physiological functions. The capacity to transmit extracellular signals and the extent of cellular response are largely determined by the amount of functional receptors at the cell surface that is subject to complex and fine-tuned regulation. Here, we demonstrate that the cell surface expression level of an inhibitory GPCR, the human δ-opioid receptor (hδOR) involved in pain and mood regulation, is modulated by site-specific N-acetylgalactosamine (GalNAc) -type O-glycosylation. Read More

    Blockade of CD38 diminishes lipopolysaccharide-induced macrophage classical activation and acute kidney injury involving NF-κB signaling suppression.
    Cell Signal 2017 Nov 11;42:249-258. Epub 2017 Nov 11.
    Center for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, PR China. Electronic address:
    The CD38, possessing ADP-ribosyl cyclase (ADPR-cyclase) and cyclic ADP-ribose hydrolase (cADPR-hydrolase), is able to regulate a variety of cellular activities. However, the role and mechanisms for CD38 in macrophage activation and sepsis-induced acute kidney injury (AKI) remain to be determined. Here we report that in cultured macrophages, Lipopolysaccharide (LPS) could upregulate CD38 expression in time and dose dependent manner. Read More

    Optogenetic control of focal adhesion kinase signaling.
    Cell Signal 2017 Oct 23;42:176-183. Epub 2017 Oct 23.
    Faculty of Biology, University of Freiburg, Schaenzlestr. 1, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Schaenzlestr. 18, 79104 Freiburg, Germany. Electronic address:
    Focal adhesion kinase (FAK) integrates signaling from integrins, growth factor receptors and mechanical stress to control cell adhesion, motility, survival and proliferation. Here, we developed a single-component, photo-activatable FAK, termed optoFAK, by using blue light-induced oligomerization of cryptochrome 2 (CRY2) to activate FAK-CRY2 fusion proteins. OptoFAK functions uncoupled from physiological stimuli and activates downstream signaling rapidly and reversibly upon blue light exposure. Read More

    Uev1A-Ubc13 catalyzes K63-linked ubiquitination of RHBDF2 to promote TACE maturation.
    Cell Signal 2017 Oct 22;42:155-164. Epub 2017 Oct 22.
    Beijing Key Laboratory of DNA Damage Responses and College of Life Sciences, Capital Normal University, Beijing 100048, China; Department of Microbiology and Immunology, University of Saskatchewan, S7N 5E5, Canada. Electronic address:
    The TNFα-induced NF-κB signaling pathway plays critical roles in multiple biological processes. Extensive studies have explored the mechanisms regulating this signaling cascade, and identified an E2 complex, Uev1A-Ubc13, that mediates K63-linked poly-Ub chain formation and thus recruits NEMO to activate the signaling transduction. In this study, we demonstrate that the Uev1A-Ubc13 complex simultaneously serves as a repressor of the NF-κB pathway. Read More

    Emerging role of non-coding RNA in oral cancer.
    Cell Signal 2017 Oct 19;42:134-143. Epub 2017 Oct 19.
    Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address:
    Oral squamous cell carcinoma (OSCC) is characterized by genomic and epigenomic alterations. However, the mechanisms underlying oral squamous cell carcinoma tumorigenesis and progression remain to be elucidated. Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and extracellular RNAs (exRNAs) are emerging groups of regulatory RNAs, which possess low or no protein-coding potential. Read More

    The allosteric site regulates the voltage sensitivity of muscarinic receptors.
    Cell Signal 2017 Oct 19;42:114-126. Epub 2017 Oct 19.
    Department of Cardiovascular Physiology, Ruhr-University Bochum, Universitätsstr. 150, 44780 Bochum, Germany. Electronic address:
    Muscarinic receptors (M-Rs) for acetylcholine (ACh) belong to the class A of G protein-coupled receptors. M-Rs are activated by orthosteric agonists that bind to a specific site buried in the M-R transmembrane helix bundle. In the active conformation, receptor function can be modulated either by allosteric modulators, which bind to the extracellular receptor surface or by the membrane potential via an unknown mechanism. Read More

    Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4.
    Cell Signal 2017 Oct 16;42:88-96. Epub 2017 Oct 16.
    School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK. Electronic address:
    Cell migration towards a chemotactic stimulus relies on the re-arrangement of the cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4, breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and Jurkat T-cells. Read More

    Bromodomain protein BRD4 promotes cell proliferation in skin squamous cell carcinoma.
    Cell Signal 2017 Oct 16;42:106-113. Epub 2017 Oct 16.
    Department of Plastic Surgery, the Second Affiliated Hospital of Suzhou University, Suzhou, China. Electronic address:
    The present study examined the expression and biological functions of bromodomain-containing protein 4 (BRD4) in skin squamous cell carcinoma (SCC) cells. Our results show that BRD4 mRNA and protein expression was upregulated in human skin SCC cells, as compared to its level in the normal skin keratinocytes and fibroblasts. Treatment with BRD4 inhibitors, JQ1 and CPI203, resulted in proliferation inhibition, apoptosis and cell cycle arrest in both established (A431 cell line) and primary skin SCC cells. Read More

    Protein kinase- and lipase inhibitors of inositide metabolism deplete IP7 indirectly in pancreatic β-cells: Off-target effects on cellular bioenergetics and direct effects on IP6K activity.
    Cell Signal 2017 Oct 16;42:127-133. Epub 2017 Oct 16.
    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Electronic address:
    Inositol pyrophosphates have emerged as important regulators of many critical cellular processes from vesicle trafficking and cytoskeletal rearrangement to telomere length regulation and apoptosis. We have previously demonstrated that 5-di-phosphoinositol pentakisphosphate, IP7, is at a high level in pancreatic β-cells and is important for insulin exocytosis. To better understand IP7 regulation in β-cells, we used an insulin secreting cell line, HIT-T15, to screen a number of different pharmacological inhibitors of inositide metabolism for their impact on cellular IP7. Read More

    Regulating the regulators: Epigenetic, transcriptional, and post-translational regulation of RGS proteins.
    Cell Signal 2017 Oct 16;42:77-87. Epub 2017 Oct 16.
    Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA. Electronic address:
    Regulators of G protein signaling (RGS) are a family of proteins classically known to accelerate the intrinsic GTPase activity of G proteins, which results in accelerated inactivation of heterotrimeric G proteins and inhibition of G protein coupled receptor signaling. RGS proteins play major roles in essential cellular processes, and dysregulation of RGS protein expression is implicated in multiple diseases, including cancer, cardiovascular and neurodegenerative diseases. The expression of RGS proteins is highly dynamic and is regulated by epigenetic, transcriptional and post-translational mechanisms. Read More

    Impairment of energy sensors, SIRT1 and AMPK, in lipid induced inflamed adipocyte is regulated by Fetuin A.
    Cell Signal 2017 Oct 10;42:67-76. Epub 2017 Oct 10.
    Cellular and Molecular Endocrinology Laboratory, Centre for Advanced Studies in Zoology, School of Life Science, Visva-Bharati (A Central University), Santiniketan, India. Electronic address:
    Although several reports demonstrated that accumulation of excess lipid in adipose tissue produces defects in adipocyte which leads to the disruption of energy homeostasis causing severe metabolic problems, underlying mechanism of this event remains yet unclear. Here we demonstrate that FetuinA (FetA) plays a critical role in the impairment of two metabolic sensors, SIRT1 and AMPK, in inflamed adipocytes of high fat diet (HFD) mice. A linear increase in adipocyte hypertrophy from 10 to 16 week was in tandem with the increase in FetA and that coincided with SIRT1 cleavage and decrease in pAMPK which adversely affects PGC1α activation. Read More

    Proteomic analyses of signalling complexes associated with receptor tyrosine kinase identify novel members of fibroblast growth factor receptor 3 interactome.
    Cell Signal 2017 Oct 13;42:144-154. Epub 2017 Oct 13.
    Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic; Department of Human Genetics and Orthopaedic Surgery, University of California Los Angeles, California 90095, USA. Electronic address:
    Receptor tyrosine kinases (RTKs) form multiprotein complexes that initiate and propagate intracellular signals and determine the RTK-specific signalling patterns. Unravelling the full complexity of protein interactions within the RTK-associated complexes is essential for understanding of RTK functions, yet it remains an understudied area of cell biology. We describe a comprehensive approach to characterize RTK interactome. Read More

    Tubulin-dependent secretion of S100A6 and cellular signaling pathways activated by S100A6-integrin β1 interaction.
    Cell Signal 2017 Oct 8;42:21-29. Epub 2017 Oct 8.
    Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland. Electronic address:
    S100A6 is a calcium binding protein expressed mainly in fibroblasts and epithelial cells. Interestingly, S100A6 is also present in extracellular fluids. Recently we have shown that S100A6 is secreted by WJMS cells and binds to integrin β1 (Jurewicz et al. Read More

    KiSS1 gene as a novel mediator of TGFβ-mediated cell invasion in triple negative breast cancer.
    Cell Signal 2017 Oct 6;42:1-10. Epub 2017 Oct 6.
    Department of Medicine, McGill University Health Center, Cancer Research Program, Montreal, QC, H4A 3J1, Canada. Electronic address:
    The invasive and metastatic phenotypes of breast cancer correlate with high recurrence rates and poor survival outcomes. Transforming growth factor-β (TGFβ) promotes tumor progression and metastasis in aggressive breast cancer. Here, we identified the kisspeptin KiSS1 as a downstream target of canonical TGFβ/Smad2 pathway in triple negative breast cancer cells. Read More

    KLF4 overcomes tamoxifen resistance by suppressing MAPK signaling pathway and predicts good prognosis in breast cancer.
    Cell Signal 2017 Oct 4;42:165-175. Epub 2017 Oct 4.
    Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, China. Electronic address:
    Tamoxifen resistance represents a daunting challenge to the successful treatment for breast cancer. Krüppel-like factor 4 has critical roles in the development and progression of breast cancer, but its expression, function and regulation in the efficacy of TAM therapy in breast cancer have yet to be investigated. Here, we examined the clinical significance and biologic effects of KLF4 in breast cancer. Read More

    A cellular threshold for active ERK1/2 levels determines Raf/MEK/ERK-mediated growth arrest versus death responses.
    Cell Signal 2017 Oct 3;42:11-20. Epub 2017 Oct 3.
    Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address:
    In addition to its conventional role for cell proliferation and survival, the Raf/MEK/Extracellular signal-regulated kinase (ERK) pathway can also induce growth arrest and death responses, if aberrantly activated. Here, we determined a molecular basis of ERK1/2 signaling that underlies these growth inhibitory physiological outputs. We found that overexpression of ERK1 or ERK2 switches ΔRaf-1:ER-induced growth arrest responses to caspase-dependent apoptotic death responses in different cell types. Read More

    miR-216b enhances the efficacy of vemurafenib by targeting Beclin-1, UVRAG and ATG5 in melanoma.
    Cell Signal 2017 Oct 2;42:30-43. Epub 2017 Oct 2.
    School of Life Science, Beijing Institute of Technology, Beijing 100081, China. Electronic address:
    Autophagy maintains cells survival in many stressful conditions including starvation, growth factor deprivation and misfolded protein accumulation. Additionally, autophagic survival mechanisms are used by transformed tumor cells to inhibit cell death, limit drug effectiveness and possibly generate drug resistance. However, the mechanism of how cells utilize autophagy during drug resistance is not fully understood. Read More

    The PPARγ agonist rosiglitazone promotes the induction of brite adipocytes, increasing β-adrenoceptor-mediated mitochondrial function and glucose uptake.
    Cell Signal 2017 Sep 29;42:54-66. Epub 2017 Sep 29.
    Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Monash University, Parkville, Victoria 3052, Australia; Department of Pharmacology, 9 Ancora Imparo Way, Monash University, Clayton, Victoria 3800, Australia. Electronic address:
    Recruitment and activation of brite (or beige) adipocytes has been advocated as a potential avenue for manipulating whole-body energy expenditure. Despite numerous studies illustrating the differences in gene and protein markers between brown, brite and white adipocytes, there is very little information on the adrenergic regulation and function of these brite adipocytes. We have compared the functional (cyclic AMP accumulation, oxygen consumption rates, mitochondrial function, glucose uptake, extracellular acidification rates, calcium influx) profiles of mouse adipocytes cultured from three contrasting depots, namely interscapular brown adipose tissue, and inguinal or epididymal white adipose tissues, following chronic treatment with the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone. Read More

    High mobility group B1 up-regulates angiogenic and fibrogenic factors in human retinal pigment epithelial ARPE-19 cells.
    Cell Signal 2017 Dec 29;40:248-257. Epub 2017 Sep 29.
    Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; Department of Medical Laboratory Science, I-Shou University, Kaohsiung, Taiwan. Electronic address:
    Hypoxia-induced retinal neovascularization plays a central role in the pathogenesis of diabetic retinopathy. This study aimed to investigate whether hypoxia leads to the release of nuclear high mobility group box 1 (HMGB1) peptides from cultured retinal pigment epithelial ARPE-19 cells, to determine the effect of HMGB1 on angiogenic cytokine production and elucidate the involved signaling pathways. A chemical hypoxia mimetic agent, cobalt chloride, induced SIRT1 downregulation, HMGB1 nucleocytoplasmic relocation and extracellular release from ARPE-19 cells, implicating its autocrine function. Read More

    Metformin triggers apoptosis in PEL cells and alters bortezomib-induced Unfolded Protein Response increasing its cytotoxicity and inhibiting KSHV lytic cycle activation.
    Cell Signal 2017 Dec 28;40:239-247. Epub 2017 Sep 28.
    Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, 00161 Rome, Italy. Electronic address:
    Metformin, the most used drug for the treatment of diabetes type 2 patients, has been shown to have anti-cancer properties. In this study, we found that metformin induced apoptosis in Primary Effusion Lymphoma (PEL) cells, an aggressive B cell lymphoma associated with KSHV against which the conventional therapies usually fail. The cytotoxic effect of metformin correlated with intracellular reactive oxygen species reduction, activation of AMPK, the inhibition of pro-survival pathways such as mTOR and STAT3 and the down-regulation of v-FLIP, a latent viral antigen that also plays a pivotal role in PEL cell survival. Read More

    E2F6 protein levels modulate drug induced apoptosis in cardiomyocytes.
    Cell Signal 2017 Dec 28;40:230-238. Epub 2017 Sep 28.
    University of Ottawa, Department of Cellular and Molecular Medicine, Ottawa, ON, Canada; University of Ottawa Heart Institute, Ottawa, ON, Canada. Electronic address:
    The E2F/Rb pathway regulates cell growth, differentiation, and death. In particular, E2F1 promotes apoptosis in all cells including those of the heart. E2F6, which represses E2F activity, was found to induce dilated cardiomyopathy in the absence of apoptosis in murine post-natal heart. Read More

    Dephosphorylation is the mechanism of fibroblast growth factor inhibition of guanylyl cyclase-B.
    Cell Signal 2017 Dec 28;40:222-229. Epub 2017 Sep 28.
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, USA; Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA. Electronic address:
    Activating mutations in fibroblast growth factor receptor 3 (FGFR3) and inactivating mutations of guanylyl cyclase-B (GC-B, also called NPRB or NPR2) cause dwarfism. FGF exposure inhibits GC-B activity in a chondrocyte cell line, but the mechanism of the inactivation is not known. Here, we report that FGF exposure causes dephosphorylation of GC-B in rat chondrosarcoma cells, which correlates with a rapid, potent and reversible inhibition of C-type natriuretic peptide-dependent activation of GC-B. Read More

    Logarithmic expansion of LGR5(+) cells in human colorectal cancer.
    Cell Signal 2017 Sep 25;42:97-105. Epub 2017 Sep 25.
    Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Electronic address:
    Stem cells of the small and large intestine are marked by expression of the Wnt target gene LGR5, a leucine-rich-repeat-containing G protein-coupled receptor. Previous studies reported increased expression of LGR5 in human colorectal cancer (CRC) compared to normal tissue either by immunohistochemistry or in situ hybridization (ISH). However, as these studies were semi-quantitative they did not provide a numerical estimate of the magnitude of this effect. Read More

    Tyrosines-740/751 of PDGFRβ contribute to the activation of Akt/Hif1α/TGFβ nexus to drive high glucose-induced glomerular mesangial cell hypertrophy.
    Cell Signal 2017 Sep 23;42:44-53. Epub 2017 Sep 23.
    Department of Medicine, UT Health at San Antonio, TX, United States; VA Biomedical Laboratory Research, South Texas Veterans Health Care System, San Antonio, TX, United States; Geriatric Research, Education and Clinical Research, South Texas Veterans Health Care System, San Antonio, TX, United States. Electronic address:
    Glomerular mesangial cell hypertrophy contributes to the complications of diabetic nephropathy. The mechanism by which high glucose induces mesangial cell hypertrophy is poorly understood. Here we explored the role of the platelet-derived growth factor receptor-β (PDGFRβ) tyrosine kinase in driving the high glucose-induced mesangial cell hypertrophy. Read More

    Loss of Reelin protects mice against arterial thrombosis by impairing integrin activation and thrombus formation under high shear conditions.
    Cell Signal 2017 Dec 21;40:210-221. Epub 2017 Sep 21.
    Department of Vascular and Endovascular Surgery, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany. Electronic address:
    Reelin is a secreted glycoprotein and essential for brain development and plasticity. Recent studies provide evidence that Reelin modifies platelet actin cytoskeletal dynamics. In this study we sought to dissect the contribution of Reelin in arterial thrombus formation. Read More

    Interleukin 1 β-induced SMAD2/3 linker modifications are TAK1 dependent and delay TGFβ signaling in primary human mesenchymal stem cells.
    Cell Signal 2017 Dec 21;40:190-199. Epub 2017 Sep 21.
    Radboud University Medical Center, Department of Rheumatology, Experimental Rheumatology, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address:
    Background: Chondrogenic differentiation of mesenchymal stem cells (MSC) requires transforming growth factor beta (TGFβ) signaling. TGFβ binds to the type I receptor activin-like kinase (ALK)5 and results in C-terminal SMAD2/3 phosphorylation (pSMAD2/3C). In turn pSMAD2/3C translocates to the nucleus and regulates target gene expression. Read More

    Elucidating structural and molecular mechanisms of β-arrestin-biased agonism at GPCRs via MS-based proteomics.
    Cell Signal 2017 Sep 20. Epub 2017 Sep 20.
    Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong 250012, China.
    The discovery of β-arrestin-dependent GPCR signaling has led to an exciting new field in GPCR pharmacology: to develop "biased agonists" that can selectively target a specific downstream signaling pathway that elicits beneficial therapeutic effects without activating other pathways that elicit negative side effects. This new trend in GPCR drug discovery requires us to understand the structural and molecular mechanisms of β-arrestin-biased agonism, which largely remain unclear. We have used cutting-edge mass spectrometry (MS)-based proteomics, combined with systems, chemical and structural biology to study protein function, macromolecular interaction, protein expression and posttranslational modifications in the β-arrestin-dependent GPCR signaling. Read More

    AIPL1: A specialized chaperone for the phototransduction effector.
    Cell Signal 2017 Dec 20;40:183-189. Epub 2017 Sep 20.
    Department of Molecular Physiology and Biophysics, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States; Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States. Electronic address:
    Molecular chaperones play pivotal roles in protein folding, quality control, assembly of multimeric protein complexes, protein trafficking, stress responses, and other essential cellular processes. Retinal photoreceptor rod and cone cells have an unusually high demand for production, quality control, and trafficking of key phototransduction components, and thus, require a robust and specialized chaperone machinery to ensure the fidelity of sensing and transmission of visual signals. Misfolding and/or mistrafficking of photoreceptor proteins are known causes for debilitating blinding diseases. Read More

    Protein kinase C-eta regulates Mcl-1 level via ERK1.
    Cell Signal 2017 Dec 20;40:166-171. Epub 2017 Sep 20.
    Institute for Molecular Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA. Electronic address:
    Protein kinase C (PKC)-eta (PKCη) is a member of the novel category of PKC family. It is overexpressed in breast cancer and was shown to inhibit apoptosis and contribute to chemoresistance. Since the anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance, we investigated if PKCη regulates Mcl-1 level. Read More

    New kids on the block: The Popeye domain containing (POPDC) protein family acting as a novel class of cAMP effector proteins in striated muscle.
    Cell Signal 2017 Dec 20;40:156-165. Epub 2017 Sep 20.
    Developmental Dynamics, Myocardial Function, National Heart and Lung Institute, Imperial College London, United Kingdom.
    The cyclic 3',5'-adenosine monophosphate (cAMP) signalling pathway constitutes an ancient signal transduction pathway present in prokaryotes and eukaryotes. Previously, it was thought that in eukaryotes three effector proteins mediate cAMP signalling, namely protein kinase A (PKA), exchange factor directly activated by cAMP (EPAC) and the cyclic-nucleotide gated channels. However, recently a novel family of cAMP effector proteins emerged and was termed the Popeye domain containing (POPDC) family, which consists of three members POPDC1, POPDC2 and POPDC3. Read More

    GPCRs: Emerging anti-cancer drug targets.
    Cell Signal 2017 Sep 18. Epub 2017 Sep 18.
    The Scripps Research Institute, Department of Molecular Medicine, 130 Scripps Way, Jupiter, FL 33458, United States. Electronic address:
    G protein-coupled receptors (GPCRs) constitute the largest and most diverse protein family in the human genome with over 800 members identified to date. They play critical roles in numerous cellular and physiological processes, including cell proliferation, differentiation, neurotransmission, development and apoptosis. Consequently, aberrant receptor activity has been demonstrated in numerous disorders/diseases, and as a result GPCRs have become the most successful drug target class in pharmaceuticals treating a wide variety of indications such as pain, inflammation, neurobiological and metabolic disorders. Read More

    The role of A-kinase anchoring proteins in cancer development.
    Cell Signal 2017 Dec 18;40:143-155. Epub 2017 Sep 18.
    Département de Pharmacologie et de Toxicologie, Faculté de Biologie et de Médecine, Lausanne 1005, Switzerland.. Electronic address:
    Cancer development is a multifactorial process resulting from the aberrant activation of multiple signaling pathways. It has become increasingly clear that the coordination of the signaling events leading to cancer formation and progression is under the control of macromolecular transduction complexes organized by scaffolding proteins. A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins involved in the spatio-temporal activation of pathways controlling cancer cell proliferation, cell survival, and invasion. Read More

    FGD5 sustains vascular endothelial growth factor A (VEGFA) signaling through inhibition of proteasome-mediated VEGF receptor 2 degradation.
    Cell Signal 2017 Dec 18;40:125-132. Epub 2017 Sep 18.
    Dept. of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Electronic address:
    The complete repertoire of endothelial functions elicited by FGD5, a guanine nucleotide exchange factor activating the Rho GTPase Cdc42, has yet to be elucidated. Here we explore FGD5's importance during vascular endothelial growth factor A (VEGFA) signaling via VEGF receptor 2 (VEGFR2) in human endothelial cells. In microvascular endothelial cells, FGD5 is located at the inner surface of the cell membrane as well as at the outer surface of EEA1-positive endosomes carrying VEGFR2. Read More

    The C1 domain of Vav3, a novel potential therapeutic target.
    Cell Signal 2017 Dec 18;40:133-142. Epub 2017 Sep 18.
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address:
    Vav1/2/3 comprise a protein family with guanyl nucleotide exchange activity for Rho and Rac as well as with motifs conferring adapter activity. Biologically, Vav1 plays a critical role in hematologic cell signaling, whereas Vav2/3 have a wider tissue distribution, but all 3 Vav proteins are implicated in cancer development. A structural feature of Vav1/2/3 is the presence of an atypical C1 domain, which possesses close structural homology to the typical C1 domains of protein kinase C but which fails to bind the second messenger diacylglycerol or the potent analogs, the phorbol esters. Read More

    Cocaine modulates allosteric D2-σ1 receptor-receptor interactions on dopamine and glutamate nerve terminals from rat striatum.
    Cell Signal 2017 Dec 18;40:116-124. Epub 2017 Sep 18.
    Department of Life Sciences and Biotechnology (SVEB), University of Ferrara, Ferrara, Italy. Electronic address:
    The effects of nanomolar cocaine concentrations, possibly not blocking the dopamine transporter activity, on striatal D2-σ1 heteroreceptor complexes and their inhibitory signaling over Gi/o, have been tested in rat striatal synaptosomes and HEK293T cells. Furthermore, the possible role of σ1 receptors (σ1Rs) in the cocaine-provoked amplification of D2 receptor (D2R)-induced reduction of K(+)-evoked [(3)H]-DA and glutamate release from rat striatal synaptosomes, has also been investigated. The dopamine D2-likeR agonist quinpirole (10nM-1μM), concentration-dependently reduced K(+)-evoked [(3)H]-DA and glutamate release from rat striatal synaptosomes. Read More

    Diindolylmethane and its halogenated derivatives induce protective autophagy in human prostate cancer cells via induction of the oncogenic protein AEG-1 and activation of AMP-activated protein kinase (AMPK).
    Cell Signal 2017 Dec 18;40:172-182. Epub 2017 Sep 18.
    INRS-Institut Armand-Frappier, Laval, QC, Canada. Electronic address:
    3,3'-Diindolylmethane (DIM) and its synthetic halogenated derivatives 4,4'-Br2- and 7,7'-Cl2DIM (ring-DIMs) have recently been shown to induce protective autophagy in human prostate cancer cells. The mechanisms by which DIM and ring-DIMs induce autophagy have not been elucidated. As DIM is a mitochondrial ATP-synthase inhibitor, we hypothesized that DIM and ring-DIMs induce autophagy via alteration of intracellular AMP/ATP ratios and activation of AMP-activated protein kinase (AMPK) signaling in prostate cancer cells. Read More

    Glucose elicits serine/threonine kinase VRK1 to phosphorylate nuclear pregnane X receptor as a novel hepatic gluconeogenic signal.
    Cell Signal 2017 Dec 12;40:200-209. Epub 2017 Sep 12.
    Pharmacogenetics Section, Reproductive and Developmental Biology Laboratory, National Institute of Environmental Sciences, National Institutes of Health, Research Triangle Park, NC 27709, United States. Electronic address:
    Low glucose stimulated phosphorylation of pregnane X receptor (PXR) at Ser(350) in correlation with an increased gluconeogenesis in human hepatoma-derived HepG2 cells. Only glucose, but neither insulin nor glucagon, stimulated this phosphorylation. Here, serine/threonine kinase, vaccinia related kinase 1 (VRK1)-mediated phosphorylation of PXR is now defined as this glucose-elicited novel signal. Read More

    Recent development of signaling pathways inhibitors of melanogenesis.
    Cell Signal 2017 Dec 12;40:99-115. Epub 2017 Sep 12.
    College of Pharmacy and Institute of Drug Research and Development, Chungnam National, University, Daejeon 34134, Republic of Korea.
    Human skin, eye and hair color rely on the production of melanin, depending on its quantity, quality, and distribution, Melanin plays a monumental role in protecting the skin against the harmful effect of ultraviolet radiation and oxidative stress from various environmental pollutants. However, an excessive production of melanin causes serious dermatological problems such as freckles, solar lentigo (age spots), melasma, as well as cancer. Hence, the regulation of melanin production is important for controlling the hyper-pigmentation. Read More

    Fibroblast-derived HGF drives acinar lung cancer cell polarization through integrin-dependent RhoA-ROCK1 inhibition.
    Cell Signal 2017 Dec 6;40:91-98. Epub 2017 Sep 6.
    Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, United Kingdom; The CRUK Beatson Institute, Glasgow G61 1BD, United Kingdom. Electronic address:
    The formation of lumens in epithelial tissues requires apical-basal polarization of cells, and the co-ordination of this individual polarity collectively around a contiguous lumen. Signals from the Extracellular Matrix (ECM) instruct epithelia as to the orientation of where basal, and thus consequently apical, surfaces should be formed. We report that this pathway is normally absent in Calu-3 human lung adenocarcinoma cells in 3-Dimensional culture, but that paracrine signals from MRC5 lung fibroblasts can induce correct orientation of polarity and acinar morphogenesis. Read More

    MAPK activation patterns of AT1R and CB1R in SHR versus Wistar astrocytes: Evidence of CB1R hypofunction and crosstalk between AT1R and CB1R.
    Cell Signal 2017 Dec 5;40:81-90. Epub 2017 Sep 5.
    Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, United States. Electronic address:
    Background: Angiotensin (Ang) II and cannabinoids regulate physiologically relevant astroglial functions via receptor-mediated activation of Mitogen-activated protein kinases (MAPKs). In this study, we investigated the consequences of astroglial Ang II type 1 receptor (AT1R) and Cannabinoid type 1 receptor (CB1R) activation, alone and in combination, on MAPK activation in the presence and absence of hypertensive states. In addition, we also investigated a novel unidirectional crosstalk mechanism between AT1R and CB1R, that involves PKC-mediated phosphorylation of CB1R. Read More

    t-Darpp stimulates protein kinase A activity by forming a complex with its RI regulatory subunit.
    Cell Signal 2017 Dec 1;40:53-61. Epub 2017 Sep 1.
    Department of Cancer Biology, City of Hope, 1500 East Duarte Road, Duarte, CA 91107, USA. Electronic address:
    t-Darpp is the truncated form of the dopamine- and cAMP-regulated phosphoprotein of 32kDa (Darpp-32) and has been demonstrated to confer resistance to trastuzumab, a Her2-targeted anticancer agent, via sustained signaling through the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt pathway and activation of protein kinase A (PKA). The mechanism of t-Darpp-mediated PKA activation is poorly understood. In the PKA holoenzyme, when the catalytic subunits are bound to regulatory subunits RI or RII, kinase activity is inhibited. Read More

    Identification and characterization of a potent and biologically-active PDE4/7 inhibitor via fission yeast-based assays.
    Cell Signal 2017 Dec 1;40:73-80. Epub 2017 Sep 1.
    Biology Department, Boston College, 140 Commonwealth Ave., Chestnut Hill, MA 02467, USA. Electronic address:
    We previously constructed a collection of fission yeast strains that express various mammalian cyclic nucleotide phosphodiesterases (PDEs) and developed a cell-based high throughput screen (HTS) for small molecule PDE inhibitors. Here we describe a compound, BC54, that is a selective inhibitor of enzymes from the cAMP-specific PDE4 and PDE7 families. Consistent with the biological effect of other PDE4 and PDE7 inhibitors, BC54 displays potent anti-inflammatory properties and is superior to a combination of rolipram (a PDE4 inhibitor) and BRL50481 (a PDE7A inhibitor) for inducing apoptosis in chronic lymphocytic leukemia (CLL) cells. Read More

    Store-operated calcium entry is dispensable for the activation of ERK1/2 pathway in prostate cancer cells.
    Cell Signal 2017 Dec 31;40:44-52. Epub 2017 Aug 31.
    Department of Cell Biology, School of Medicine and Institute of Molecular Pathology and Biomarkers, University of Extremadura, Badajoz 06006, Spain. Electronic address:
    STIM1, the endoplasmic reticulum Ca(2+) sensor that modulates the activity of plasma membrane Ca(2+) channels, becomes phosphorylated at ERK1/2 target sites during Ca(2+) store depletion triggered by thapsigargin or epidermal growth factor (EGF). This ERK1/2-dependent phosphorylation regulates STIM1 localization and dissociation from microtubules, and it is known that enhances the binding to ORAI1, a store-operated Ca(2+) entry (SOCE) channel, leading to the activation of this Ca(2+) influx pathway. However, there remained some evidence of a role for SOCE in the activation of ERK1/2, and here we assessed the contribution of SOCE to ERK1/2 activation by generating a STIM1-deficient cell line by CRISPR/Cas9 genome editing of the STIM1 locus in prostate cancer PC3 cells. Read More

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