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https://www.readbyqxmd.com/read/28295876/a-vicious-partnership-between-akt-and-phlda3-to-facilitate-neuroendocrine-tumors
#1
Masahiro Takikawa, Rieko Ohki
Neuroendocrine tumors (NETs) are rare cancers that generally have a poor prognosis. Accurate diagnosis and proper treatment of these tumors requires a better understanding of the molecular mechanisms underlying the development of NETs. It has been shown that the mTOR inhibitor everolimus can improve the progression-free survival of pancreatic NET (PanNET) patients, suggesting that inhibition of the PI3K-Akt-mTOR pathway may suppress the progression of PanNETs. PHLDA3 is a novel tumor suppressor protein that inhibits Akt activation by competition for binding to PIP3 ...
March 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28292823/correction-annular-pip3-accumulation-controls-actin-architecture-and-modulates-cytotoxicity-at-the-immunological-synapse
#2
Audrey Le Floc'h, Yoshihiko Tanaka, Niels S Bantilan, Guillaume Voisinne, Grégoire Altan-Bonnet, Yoshinori Fukui, Morgan Huse
No abstract text is available yet for this article.
March 14, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28287114/regulation-of-inflammation-and-tumorigenesis-by-the-tipe-family-of-phospholipid-transfer-proteins
#3
REVIEW
Jason R Goldsmith, Youhai H Chen
The TIPE (tumor necrosis factor-α-induced protein 8-like) family are newly described regulators of immunity and tumorigenesis consisting of four highly homologous mammalian proteins: TNFAIP8 (tumor necrosis factor-α-induced protein 8), TIPE1 (TNFAIP8-like 1, or TNFAIP8L1), TIPE2 (TNFAIP8L2) and TIPE3 (TNFAIP8L3). They are the only known transfer proteins of the lipid secondary messengers PIP2 (phosphatidylinositol 4,5-bisphosphate) and PIP3 (phosphatidylinositol 3,4,5-trisphosphate). Cell-surface receptors, such as G-protein-coupled receptors and receptor tyrosine kinases, regulate inflammation and cancer via several signaling pathways, including the nuclear factor (NF)-κB and phosphoinositide-3 kinase (PI3K) pathways, the latter of which is upstream of both Akt and STAT3 activation...
March 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28263967/characterization-of-pten-mutations-in-brain-cancer-reveals-that-pten-mono-ubiquitination-promotes-protein-stability-and-nuclear-localization
#4
Jr-M Yang, P Schiapparelli, H-N Nguyen, A Igarashi, Q Zhang, S Abbadi, L M Amzel, H Sesaki, A Quiñones-Hinojosa, M Iijima
PTEN is a PIP3 phosphatase that antagonizes oncogenic PI3-kinase signalling. Due to its critical role in suppressing the potent signalling pathway, it is one of the most mutated tumour suppressors, especially in brain tumours. It is generally thought that PTEN deficiencies predominantly result from either loss of expression or enzymatic activity. By analysing PTEN in malignant glioblastoma primary cells derived from 16 of our patients, we report mutations that block localization of PTEN at the plasma membrane and nucleus without affecting lipid phosphatase activity...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28250113/cxcl12-induced-macropinocytosis-modulates-two-distinct-pathways-to-activate-mtorc1-in-macrophages
#5
Regina Pacitto, Isabella Gaeta, Joel A Swanson, Sei Yoshida
Although growth factors and chemokines elicit different overall effects on cells-growth and chemotaxis, respectively-and activate distinct classes of cell-surface receptors, nonetheless, they trigger similar cellular activities and signaling pathways. The growth factor M-CSF and the chemokine CXCL12 both stimulate the endocytic process of macropinocytosis, and both activate the mechanistic target of rapamycin complex 1 (mTORC1), a protein complex that regulates cell metabolism. Recent studies of signaling by M-CSF in macrophages identified a role for macropinocytosis in the activation of mTORC1, in which delivery of extracellular amino acids into lysosomes via macropinocytosis was required for activation of mTORC1...
March 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28248320/non-coding-rna-the-cancer-link-rna-between-pip3-and-akt
#6
Eytan Zlotorynski
No abstract text is available yet for this article.
March 1, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28247964/pi-3-4-p2-plays-critical-roles-in-the-regulation-of-focal-adhesion-dynamics-of-mda-mb-231-breast-cancer-cells
#7
Miki Fukumoto, Takeshi Ijuin, Tadaomi Takenawa
Phosphoinositides play pivotal roles in the regulation of cancer cell phenotypes. Among them, phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2 ) localizes to the invadopodia, and positively regulates tumor cell invasion. In this study, we examined the effect of PI(3,4)P2 on focal adhesion dynamics in MDA-MB-231 basal breast cancer cells. Knockdown of SHIP2, a phosphatidylinositol 3,4,5-trisphosphatase (PIP3 ) 5-phosphatase that generates PI(3,4)P2 , in MDA-MB-231 breast cancer cells, induced the development of focal adhesions and cell spreading, leading to the suppression of invasion...
March 1, 2017: Cancer Science
https://www.readbyqxmd.com/read/28247205/the-mechanism-of-jurkat-cells-apoptosis-induced-by-aggregatibacter-actinomycetemcomitans-cytolethal-distending-toxin
#8
Hui-Ping Chen, Lu Li, Xu Chen, Mi-Fang Yang, Yu Ye, Xiao-Qian Wang, Yan Xu
Cytolethal distending toxin (CDT) which is produced by Aggregatibacter actinomycetemcomitans causes apoptosis in lymphocytes. But the specific mechanism is not clear. The aim of our research was to investigate the effect and mechanism during this process. The wild-type CdtA, CdtB, CdtC (CdtA(W), CdtB(W), CdtC(W)) and mutant CdtB (CdtB(M)) were expressed and purified respectively and the purity of each subunit was examined by BandScan software. And the type I deoxyribonuclease and PI-3,4,5-triphosphate (PI-3,4,5-P3, PIP3) phosphatase activity were detected by DNA agarose gel electrophoresis and enzyme-linked immunosorbent assay respectively...
February 28, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28218907/the-link-a-lncrna-interacts-with-ptdins-3-4-5-p3-to%C3%A2-hyperactivate-akt%C3%A2-and-confer-resistance-to-akt%C3%A2-inhibitors
#9
Aifu Lin, Qingsong Hu, Chunlai Li, Zhen Xing, Guolin Ma, Cheng Wang, Jun Li, Yin Ye, Jun Yao, Ke Liang, Shouyu Wang, Peter K Park, Jeffrey R Marks, Yan Zhou, Jianwei Zhou, Mien-Chie Hung, Han Liang, Zhibin Hu, Hongbing Shen, David H Hawke, Leng Han, Yubin Zhou, Chunru Lin, Liuqing Yang
Phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3 or PIP3) mediates signalling pathways as a second messenger in response to extracellular signals. Although primordial functions of phospholipids and RNAs have been hypothesized in the 'RNA world', physiological RNA-phospholipid interactions and their involvement in essential cellular processes have remained a mystery. We explicate the contribution of lipid-binding long non-coding RNAs (lncRNAs) in cancer cells. Among them, long intergenic non-coding RNA for kinase activation (LINK-A) directly interacts with the AKT pleckstrin homology domain and PIP3 at the single-nucleotide level, facilitating AKT-PIP3 interaction and consequent enzymatic activation...
March 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28196852/inpp4b-and-pten-loss-leads-to-pi-3-4-p2-accumulation-and-inhibition-of-pi3k-in-tnbc
#10
Darien E Reed, Kevan M Shokat
Triple-negative breast cancer [TNBC, lacks expression of estrogen receptor (ER), progesterone receptor (PR) and amplification of HER2/Neu] remains one of the most aggressive subtypes, affects the youngest patients and still lacks an effective targeted therapy(1,2). Both phosphatidylinositol-3-kinase (PI3K)-α and -β contribute to oncogenesis of solid tumors, including the development of breast cancer(3). Inositol polyphosphate-4-phosphatase type II (INPP4B) catalyzes the removal of the 4'-phosphate of phosphatidylinositol-(3,4-bisphosphate (PI-3,4-P2) creating phosphatidylinositol-3-phosphate(4)...
February 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28174296/ncs1-regulates-ca2-dependent-focal-exocytosis-of-golgi-derived-vesicles-to-help-phagocytic-uptake-in-macrophages
#11
Nimi Vashi, Syed Bilal Ahmad Andrabi, Swapnil Ghanwat, Mrutyunjay Suar, Dhiraj Kumar
During phagocytic uptake by macrophages, role of Golgi apparatus was previously ruled out. Notably all such reports were limited to Fcγ-receptor mediated phagocytosis. Here we unravel a highly devolved mechanism for recruitment of Golgi-derived secretory vesicles during phagosome biogenesis, which was important for uptake of most cargos except IgG-coated ones. We report recruitment of Mannosidase-II positive Golgi-derived vesicles during uptake of diverse targets including latex beads, E. coli, Salmonella Typhimurium and Mycobacterium tuberculosis in human and mouse macrophages...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28157504/pi-3-4-5-p3-engagement-restricts-akt-activity-to-cellular-membranes
#12
Michael Ebner, Iva Lučić, Thomas A Leonard, Ivan Yudushkin
Protein kinase B/Akt regulates cellular metabolism, survival, and proliferation in response to hormones and growth factors. Hyperactivation of Akt is frequently observed in cancer, while Akt inactivation is associated with severe diabetes. Here, we investigated the molecular and cellular mechanisms that maintain Akt activity proportional to the activating stimulus. We show that binding of phosphatidylinositol-3,4,5-trisphosphate (PIP3) or PI(3,4)P2 to the PH domain allosterically activates Akt by promoting high-affinity substrate binding...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28136018/co-existence-of-ras-activation-in-a-chemotactic-signal-transduction-pathway-and-in-an-autonomous-wave-forming-system
#13
Mary Ecke, Günther Gerisch
The activation of Ras is common to two activities in cells of Dictyostelium discoideum: the directed movement in a gradient of chemoattractant and the autonomous generation of propagating waves of actin polymerization on the substrate-attached cell surface. We produced large cells by electric-pulse induced fusion to simultaneously study both activities in one cell. For imaging, a fluorescent label for activated Ras was combined with labels for filamentous actin, PIP3, or PTEN. Chemotactic responses were elicited in a diffusion gradient of cyclic AMP...
January 31, 2017: Small GTPases
https://www.readbyqxmd.com/read/28119806/class-i-phosphatidylinositol-3-kinase-inhibitors-for-cancer-therapy
#14
REVIEW
Wennan Zhao, Yuling Qiu, Dexin Kong
The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in human cancers. Class I PI3Ks are lipid kinases that phosphorylate phosphatidylinositol 4,5-bisphosphate (PIP2) at the 3-OH of the inositol ring to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), which in turn activates Akt and the downstream effectors like mammalian target of rapamycin (mTOR) to play key roles in carcinogenesis. Therefore, PI3K has become an important anticancer drug target, and currently there is very high interest in the pharmaceutical development of PI3K inhibitors...
January 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28106075/phosphatidylinositol-3-4-bisphosphate-regulates-neurite-initiation-and-dendrite-morphogenesis-via-actin-aggregation
#15
Shu-Xin Zhang, Li-Hui Duan, Shun-Ji He, Gui-Feng Zhuang, Xiang Yu
Neurite initiation is critical for neuronal morphogenesis and early neural circuit development. Recent studies showed that local actin aggregation underneath the cell membrane determined the site of neurite initiation. An immediately arising question is what signaling mechanism initiated actin aggregation. Here we demonstrate that local clustering of phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2), a phospholipid with relatively few known signaling functions, is necessary and sufficient for aggregating actin and promoting neuritogenesis...
February 2017: Cell Research
https://www.readbyqxmd.com/read/28063949/vitamin-d-supplementation-inhibits-oxidative-stress-and-upregulate-sirt1-ampk-glut4-cascade-in-high-glucose-treated-3t3l1-adipocytes-and-in-adipose-tissue-of-high-fat-diet-fed-diabetic-mice
#16
Prasenjit Manna, Arunkumar E Achari, Sushil K Jain
This study examined the hypothesis that vitamin-D prevents oxidative stress and upregulates glucose metabolism via activating insulin-independent signaling molecules in 3T3-L1 adipocytes and in high fat diet (HFD)-fed mice. To investigate the mechanism 3T3L1 adipocytes were treated with high glucose (HG, 25 mM) and 1,25(OH)2D3 (1,25-dihydroxyvitamin D3) (0-50 nM). Results showed that 1,25(OH)2D3 supplementation decreased NOX4 expression, ROS production, NF-κB phosphorylation, and increased the expression of Nrf2 and Trx in HG-treated cells...
February 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28018608/digenic-mutations-of-human-ocrl-paralogs-in-dent-s-disease-type-2-associated-with-chiari-i-malformation
#17
Daniel Duran, Sheng Chih Jin, Tyrone DeSpenza, Carol Nelson-Williams, Andrea G Cogal, Elizabeth W Abrash, Peter C Harris, John C Lieske, Serena Je Shimshak, Shrikant Mane, Kaya Bilguvar, Michael L DiLuna, Murat Günel, Richard P Lifton, Kristopher T Kahle
OCRL1 and its paralog INPP5B encode phosphatidylinositol 5-phosphatases that localize to the primary cilium and have roles in ciliogenesis. Mutations in OCRL1 cause the X-linked Dent disease type 2 (DD2; OMIM# 300555), characterized by low-molecular weight proteinuria, hypercalciuria, and the variable presence of cataracts, glaucoma and intellectual disability without structural brain anomalies. Disease-causing mutations in INPP5B have not been described in humans. Here, we report the case of an 11-year-old boy with short stature and an above-average IQ; severe proteinuria, hypercalciuria and osteopenia resulting in a vertebral compression fracture; and Chiari I malformation with cervico-thoracic syringohydromyelia requiring suboccipital decompression...
2016: Human Genome Variation
https://www.readbyqxmd.com/read/28003865/skin-aging-dependent-activation-of-the-pi3k-signaling-pathway-via-downregulation-of-pten-increases-intracellular-ros-in-human-dermal-fibroblasts
#18
Eun-Mi Noh, Jinny Park, Hwa-Ryung Song, Jeong-Mi Kim, Minok Lee, Hyun-Kyung Song, On-Yu Hong, Pyoung H Whang, Myung-Kwan Han, Kang-Beom Kwon, Jong-Suk Kim, Young-Rae Lee
Reactive oxygen species (ROS) play a major role in both chronological aging and photoaging. ROS induce skin aging through their damaging effect on cellular constituents. However, the origins of ROS have not been fully elucidated. We investigated that ROS generation of replicative senescent fibroblasts is generated by the modulation of phosphatidylinositol 3,4,5-triphosphate (PIP3) metabolism. Reduction of the PTEN protein, which dephosphorylates PIP3, was responsible for maintaining a high level of PIP3 in replicative cells and consequently mediated the activation of the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27960076/a-plasma-membrane-template-for-macropinocytic-cups
#19
Douwe M Veltman, Thomas D Williams, Gareth Bloomfield, Bi-Chang Chen, Eric Betzig, Robert H Insall, Robert R Kay
Macropinocytosis is a fundamental mechanism that allows cells to take up extracellular liquid into large vesicles. It critically depends on the formation of a ring of protrusive actin beneath the plasma membrane, which develops into the macropinocytic cup. We show that macropinocytic cups in Dictyostelium are organised around coincident intense patches of PIP3, active Ras and active Rac. These signalling patches are invariably associated with a ring of active SCAR/WAVE at their periphery, as are all examined structures based on PIP3 patches, including phagocytic cups and basal waves...
December 13, 2016: ELife
https://www.readbyqxmd.com/read/27933776/regulation-of-a-coupled-marcks-pi3k-lipid-kinase-circuit-by-calmodulin-single-molecule-analysis-of-a-membrane-bound-signaling-module
#20
Brian P Ziemba, G Hayden Swisher, Glenn Masson, John E Burke, Roger L Williams, Joseph J Falke
Amoeboid cells that employ chemotaxis to travel up an attractant gradient possess a signaling network assembled on the leading edge of the plasma membrane that senses the gradient and remodels the actin mesh and cell membrane to drive movement in the appropriate direction. In leukocytes such as macrophages and neutrophils, and perhaps in other amoeboid cells as well, the leading edge network includes a positive feedback loop in which the signaling of multiple pathway components is cooperatively coupled. Cytoplasmic Ca(2+) is a recently recognized component of the feedback loop at the leading edge where it stimulates phosphoinositide-3-kinase (PI3K) and the production of its product signaling lipid phosphatidylinositol 3,4,5-trisphosphate (PIP3)...
November 22, 2016: Biochemistry
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