Abstract：
:In three-dimensional matrices cancer cells move with a rounded, amoeboid morphology that is controlled by ROCK-dependent contraction of acto-myosin. In this study, we show that PDK1 is required for phosphorylation of myosin light chain and cell motility, both on deformable gels and in vivo. Depletion of PDK1 alters the localization of ROCK1 and reduces its ability to drive cortical acto-myosin contraction. This form of ROCK1 regulation does not require PDK1 kinase activity, but instead involves direct binding of PDK1 to ROCK1 at the plasma membrane; PDK1 competes directly with RhoE for binding to ROCK1. In the absence of PDK1, negative regulation by RhoE predominates, causing reduced acto-myosin contractility and motility. This work uncovers a novel non-catalytic role for PDK1 in regulating cortical acto-myosin and cell motility.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Pinner S,Sahai Edoi
10.1038/ncb1675subject
Has Abstractpub_date
2008-02-01 00:00:00pages
127-37issue
2eissn
1465-7392issn
1476-4679pii
ncb1675journal_volume
10pub_type
杂志文章abstract：:Transforming growth factor-beta (TGF-beta) induces epithelial-mesenchymal transdifferentiation (EMT) accompanied by cellular differentiation and migration. Despite extensive transcriptomic profiling, the identification of TGF-beta-inducible, EMT-specific genes has met with limited success. Here we identify a post-tran...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2029
更新日期：2010-03-01 00:00:00
abstract：:The asymmetric segregation of cell-fate determinants and the generation of daughter cells of different sizes rely on the correct orientation and position of the mitotic spindle. In the Drosophila embryo, the determinant Prospero is localized basally and is segregated equally to daughters of similar cell size during ep...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/71323
更新日期：2000-01-01 00:00:00
abstract：:The Morphogenesis and Cell Behaviour meeting held this fall in Barcelona explored the role of forces, adhesion and oscillations in embryonic morphogenesis. It highlighted the impact of new microscopy methods and modelling approaches on the most recent advances of the field. ...
journal_title：Nature cell biology
pub_type：
doi：10.1038/ncb0109-3
更新日期：2009-01-01 00:00:00
abstract：:The Drosophila fruitless (fru) gene product Fru has been postulated to be a neural sex-determination factor that directs the development of at least two male-specific characteristics, namely courtship behaviour and formation of the muscle of Lawrence (MOL). The fru gene encodes a putative transcription factor with a B...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35019537
更新日期：2000-08-01 00:00:00
abstract：:Endocytosis of cell surface receptors is an important regulatory event in signal transduction. The transforming growth factor beta (TGF-beta) superfamily signals to the Smad pathway through heteromeric Ser-Thr kinase receptors that are rapidly internalized and then downregulated in a ubiquitin-dependent manner. Here w...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb975
更新日期：2003-05-01 00:00:00
abstract：: ...
journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/s41556-018-0246-5
更新日期：2018-12-01 00:00:00
abstract：:Analysis of the mechanisms underlying cell fates requires the molecular quantification of cellular features. Classical techniques use population average readouts at single time points. However, these approaches mask cellular heterogeneity and dynamics and are limited for studying rare and heterogeneous cell population...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb3042
更新日期：2014-10-01 00:00:00
abstract：:It is now well established that stromal interaction molecule 1 (STIM1) is the calcium sensor of endoplasmic reticulum stores required to activate store-operated calcium entry (SOC) channels at the surface of non-excitable cells. However, little is known about STIM1 in excitable cells, such as striated muscle, where th...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1731
更新日期：2008-06-01 00:00:00
abstract：:Formation of a stable lamellipodium at the front of migrating cells requires localization of Rac activation to the leading edge. Restriction of alpha4 integrin phosphorylation to the leading edge limits the interaction of alpha4 with paxillin to the sides and rear of a migrating cell. The alpha4-paxillin complex inhib...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1234
更新日期：2005-04-01 00:00:00
abstract：:Nitric oxide (NO) is a pleiotropic signalling molecule that binds to cytochrome c oxidase (complex IV) reversibly and in competition with oxygen. This action of NO has both physiological and pathophysiological consequences. Here we report that endogenously generated NO, which disrupts the respiratory chain, may cause ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1188
更新日期：2004-11-01 00:00:00
abstract：:Direct reprogramming by forced expression of transcription factors can convert one cell type into another. Thus, desired cell types can be generated bypassing pluripotency. However, direct reprogramming towards renal cells remains an unmet challenge. Here, we identify renal cell fate-inducing factors on the basis of t...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3437
更新日期：2016-12-01 00:00:00
abstract：:The formation of branched epithelial networks is fundamental to the development of many organs, such as the lung, the kidney or the vasculature. Little is known about the mechanisms that control cell rearrangements during tubulogenesis and regulate the size of individual tubes. Recent studies indicate that whereas the...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1049
更新日期：2003-10-01 00:00:00
abstract：:The Notch1 gene has an important role in mammalian cell-fate decision and tumorigenesis. Upstream control mechanisms for transcription of this gene are still poorly understood. In a chemical genetics screen for small molecule activators of Notch signalling, we identified epidermal growth factor receptor (EGFR) as a ke...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1750
更新日期：2008-08-01 00:00:00
abstract：:Cancer cells consume large quantities of glucose and primarily use glycolysis for ATP production, even in the presence of adequate oxygen. This metabolic signature (aerobic glycolysis or the Warburg effect) enables cancer cells to direct glucose to biosynthesis, supporting their rapid growth and proliferation. However...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2172
更新日期：2011-03-01 00:00:00
abstract：:The Ndc80 complex (Ndc80, Nuf2, Spc24 and Spc25) is a highly conserved kinetochore protein essential for end-on anchorage to spindle microtubule plus ends and for force generation coupled to plus-end polymerization and depolymerization. Spc24/Spc25 at one end of the Ndc80 complex binds the kinetochore. The N-terminal ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3323
更新日期：2016-04-01 00:00:00
abstract：:The kinase AMPK, a sensor of cellular energy stress, has been shown to oppose the growth-promoting activity of YAP, the transcriptional co-activator downstream of the Hippo signalling pathway. This finding may help to explain why the antidiabetic drug metformin, for which AMPK is a key effector, is linked to cancer-pr...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3141
更新日期：2015-04-01 00:00:00
abstract：:During apoptosis, dying cells are swiftly removed by phagocytes. It is not fully understood how apoptotic cells are recognized by phagocytes. Here we report the identification and characterization of the Caenorhabditis elegans ttr-52 gene, which encodes a transthyretin-like protein and is required for efficient cell c...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2068
更新日期：2010-07-01 00:00:00
abstract：:Once considered to be contained, infectious diseases of bacterial origin are now making a comeback. A lack of innovative therapies and the appearance of drug-resistant pathogens are becoming increasingly serious problems. A better understanding of pathogen-host interactions at the cellular and molecular levels is nece...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/15620
更新日期：1999-11-01 00:00:00
abstract：:The Semliki Forest virus capsid protein contains a chymotrypsin-like protease domain that must fold before it can autocatalytically cleave the protein from a larger polyprotein precursor. Here we analyse this cleavage in living mammalian and prokaryotic cells, and find that it occurs immediately after the emergence of...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/14032
更新日期：1999-10-01 00:00:00
abstract：:Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule latt...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-019-0375-5
更新日期：2019-09-01 00:00:00
abstract：:Fetal haematopoietic stem cells (HSCs) self-renew extensively to build the blood system from scratch. The protein Lin28b negatively regulates the microRNA let-7 to keep levels of its target Hmga2 high, hence conferring high self-renewal potential to fetal HSCs. This regulatory circuit can be experimentally modulated t...
journal_title：Nature cell biology
pub_type： 评论,新闻
doi：10.1038/ncb2817
更新日期：2013-08-01 00:00:00
abstract：:Microtubules are central elements of the eukaryotic cytoskeleton that often function as part of branched networks. Current models for branching include nucleation of new microtubules from severed microtubule seeds or from γ-tubulin recruited to the side of a pre-existing microtubule. Here, we found that microtubules c...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-018-0199-8
更新日期：2018-10-01 00:00:00
abstract：:Actomyosin contractility is a mechanism by which cells exert locomotory force against their environment. Signalling downstream of the small GTPase Rho increases contractility through Rho-kinase (ROCK)-mediated regulation of myosin-II light chain (MLC2) phosphorylation. Cdc42 signalling has been shown to control cell p...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1230
更新日期：2005-03-01 00:00:00
abstract：:Correct placement and orientation of the mitotic spindle is essential for segregation of localized components and positioning of daughter cells. Although these processes are important in many cells, few factors that regulate spindle placement are known. Previous work has shown that GPB-1, the Gbeta subunit of a hetero...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35060092
更新日期：2001-03-01 00:00:00
abstract：:The remarkable stability of gene expression in somatic cells is exemplified by the way memory of an active gene state is retained when an endoderm cell nucleus is transplanted to an enucleated egg. Here we analyse the mechanism of a similar example of epigenetic memory. We find that memory can persist through 24 cell ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1674
更新日期：2008-01-01 00:00:00
abstract：:Cancer cells use aerobic glycolysis preferentially for energy provision and this metabolic change is important for tumour growth. Here, we have found a link between the tumour suppressor p53, the transcription factor NF-kappaB and glycolysis. In p53-deficient primary cultured cells, kinase activities of IKKalpha and I...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1724
更新日期：2008-05-01 00:00:00
abstract：:Vital organs such as the pancreas and the brain lack the capacity for effective regeneration. To overcome this limitation, an emerging strategy consists of converting resident tissue-specific cells into the cell types that are lost due to disease by a process called in vivo lineage reprogramming. Here we discuss recen...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb3108
更新日期：2015-03-01 00:00:00
abstract：:Spatial and temporal coordination of polo-like kinase 1 (Plk1) activity is necessary for mitosis and cytokinesis, and this is achieved through binding to phosphorylated docking proteins with distinct subcellular localizations. Although cyclin-dependent kinase 1 (Cdk1) creates these phosphorylated docking sites in meta...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1557
更新日期：2007-04-01 00:00:00
abstract：:The tumour stroma is an active participant during cancer progression. Stromal cells promote tumour progression and metastasis through multiple mechanisms including enhancing tumour invasiveness and angiogenesis, and suppressing immune surveillance. We report here that miR-126/miR-126(*), a microRNA pair derived from a...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2690
更新日期：2013-03-01 00:00:00
abstract：:The initial differential treatment of the two X chromosomes during X-chromosome inactivation is controlled by the X-inactivation centre (Xic). This locus determines how many X chromosomes are present in a cell ('counting') and which X chromosome will be inactivated in female cells ('choice'). Critical control sequence...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1365
更新日期：2006-03-01 00:00:00
