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851.
852.
Sei Yoshida Regina Pacitto Ken Inoki Joel Swanson 《Cellular and molecular life sciences : CMLS》2018,75(7):1227-1239
The growth and proliferation of metazoan cells are driven by cellular nutrient status and by extracellular growth factors. Growth factor receptors on cell surfaces initiate biochemical signals that increase anabolic metabolism and macropinocytosis, an actin-dependent endocytic process in which relatively large volumes of extracellular solutes and nutrients are internalized and delivered efficiently into lysosomes. Macropinocytosis is prominent in many kinds of cancer cells, and supports the growth of cells transformed by oncogenic K-Ras. Growth factor receptor signaling and the overall metabolic status of the cell are coordinated in the cytoplasm by the mechanistic target-of-rapamycin complex-1 (mTORC1), which positively regulates protein synthesis and negatively regulates molecular salvage pathways such as autophagy. mTORC1 is activated by two distinct Ras-related small GTPases, Rag and Rheb, which associate with lysosomal membranes inside the cell. Rag recruits mTORC1 to the lysosomal surface where Rheb directly binds to and activates mTORC1. Rag is activated by both lysosomal luminal and cytosolic amino acids; Rheb activation requires phosphoinositide 3-kinase, Akt, and the tuberous sclerosis complex-1/2. Signals for activation of Rag and Rheb converge at the lysosomal membrane, and several lines of evidence support the idea that growth factor-dependent endocytosis facilitates amino acid transfer into the lysosome leading to the activation of Rag. This review summarizes evidence that growth factor-stimulated macropinocytosis is essential for amino acid-dependent activation of mTORC1, and that increased solute accumulation by macropinocytosis in transformed cells supports unchecked cell growth. 相似文献
853.
854.
Se Hwan Mun Na Young Ko Hyuk Soon Kim Jie Wan Kim Do Kyun Kim A-Ram Kim Seung Hyun Lee Yong-Gil Kim Chang Keun Lee Seoung Hoon Lee Bo Kyung Kim Michael A. Beaven Young Mi Kim Wahn Soo Choi 《Cellular and molecular life sciences : CMLS》2010,67(22):3883-3892
Interleukin (IL)-33 is a recently described pro-inflammatory cytokine. Here we demonstrate IL-33 as a regulator of functional osteoclasts (OCs) from human CD14+ monocytes. IL-33 stimulates formation of tartrate-resistant acid phosphatase (TRAP)+ multinuclear OCs from monocytes. This action was suppressed by anti-ST2 antibody, suggesting that IL-33 acts through its receptor ST2, but not by the receptor activator of NF-κB ligand (RANKL) decoy, osteoprotegerin, or anti-RANKL antibody. IL-33 stimulated activating phosphorylations of signaling molecules in monocytes that are critical for OC development. These included Syk, phospholipase Cγ2, Gab2, MAP kinases, TAK-1, and NF-κB. IL-33 also enhanced expression of OC differentiation factors including TNF-α receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells cytoplasmic 1, c-Fos, c-Src, cathepsin K, and calcitonin receptor. IL-33 eventually induced bone resorption. This study suggests that the osteoclastogenic property of IL-33 is mediated through TRAF6 as well as the immunoreceptor tyrosine-based activation motif-dependent Syk/PLCγ pathway in human CD14+ monocytes. 相似文献
855.
Potassium and sodium transport in non-animal cells: the Trk/Ktr/HKT transporter family 总被引:1,自引:1,他引:0
C. Corratgé-Faillie M. Jabnoune S. Zimmermann A.-A. Véry C. Fizames H. Sentenac 《Cellular and molecular life sciences : CMLS》2010,67(15):2511-2532
Bacterial Trk and Ktr, fungal Trk and plant HKT form a family of membrane transporters permeable to K+ and/or Na+ and characterized by a common structure probably derived from an ancestral K+ channel subunit. This transporter family, specific of non-animal cells, displays a large diversity in terms of ionic permeability,
affinity and energetic coupling (H+–K+ or Na+–K+ symport, K+ or Na+ uniport), which might reflect a high need for adaptation in organisms living in fluctuating or dilute environments. Trk/Ktr/HKT
transporters are involved in diverse functions, from K+ or Na+ uptake to membrane potential control, adaptation to osmotic or salt stress, or Na+ recirculation from shoots to roots in plants. Structural analyses of bacterial Ktr point to multimeric structures physically
interacting with regulatory subunits. Elucidation of Trk/Ktr/HKT protein structures along with characterization of mutated
transporters could highlight functional and evolutionary relationships between ion channels and transporters displaying channel-like
features. 相似文献
856.
Experimental modeling is the construction of theoretical models hand in hand with experimental activity. As explained in Section 1, experimental modeling starts with claims about phenomena that use abstract concepts, concepts whose conditions of realization are not yet specified; and it ends with a concrete model of the phenomenon, a model that can be tested against data. This paper argues that this process from abstract concepts to concrete models involves judgments of relevance, which are irreducibly normative. In Section 2, we show, on the basis of several case studies, how these judgments contribute to the determination of the conditions of realization of the abstract concepts and, at the same time, of the quantities that characterize the phenomenon under study. Then, in Section 3, we compare this view on modeling with other approaches that also have acknowledged the role of relevance judgments in science. To conclude, in Section 4, we discuss the possibility of a plurality of relevance judgments and introduce a distinction between locally and generally relevant factors. 相似文献
857.
Voltage-gated calcium channels are important mediators of calcium influx into electrically excitable cells. The amount of
calcium entering through this family of channel proteins is not only determined by the functional properties of channels embedded
in the plasma membrane but also by the numbers of channels that are expressed at the cell surface. The trafficking of channels
is controlled by numerous processes, including co-assembly with ancillary calcium channel subunits, ubiquitin ligases, and
interactions with other membrane proteins such as G protein coupled receptors. Here we provide an overview about the current
state of knowledge of calcium channel trafficking to the cell membrane, and of the mechanisms regulating the stability and
internalization of this important ion channel family. 相似文献
858.
Machnicka B Grochowalska R Bogusławska DM Sikorski AF Lecomte MC 《Cellular and molecular life sciences : CMLS》2012,69(2):191-201
This review focuses on the recent advances in functions of spectrins in non-erythroid cells. We discuss new data concerning
the commonly known role of the spectrin-based skeleton in control of membrane organization, stability and shape, and tethering
protein mosaics to the cellular motors and to all major filament systems. Particular effort has been undertaken to highlight
recent advances linking spectrin to cell signaling phenomena and its participation in signal transduction pathways in many
cell types. 相似文献
859.
860.
Farooqui AA Farooqui T Panza F Frisardi V 《Cellular and molecular life sciences : CMLS》2012,69(5):741-762
The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin
resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation
in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone
released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the
hypothalamic ‘bodyweight/appetite/satiety set point,’ resulting in the initiation and development of metabolic syndrome. Metabolic
syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer’s disease. The molecular mechanism
underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However,
it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment
of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with
abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders
such as stroke, Alzheimer’s disease and depression. The purpose of this review is not only to describe the involvement of
brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical
changes in stroke, Alzheimer’s disease and depression to a wider audience of neuroscientists with the hope that this discussion
will initiate more studies on the relationship between metabolic syndrome and neurological disorders. 相似文献