Abstract:
:Members of the PAR-1/MARK kinase family play critical roles in polarity and cell cycle control and are regulated by 14-3-3 scaffolding proteins, as well as the LKB1 tumour suppressor kinase and atypical protein kinase C (PKC). In this study, we initially investigated the mechanism underlying the interaction of mammalian MARK3 with 14-3-3. We demonstrate that 14-3-3 binding to MARK3 is dependent on phosphorylation, and necessitates the phosphate-binding pocket of 14-3-3. We found that interaction with 14-3-3 was not mediated by the previously characterised MARK3 phosphorylation sites, which led us to identify 15 novel sites of phosphorylation. Single point mutation of these sites, as well as the previously identified LKB1-(T211) and the atypical PKC sites (T564/S619), did not disrupt 14-3-3 binding. However, a mutant in which all 17 phosphorylation sites had been converted to alanine residues (termed 17A-MARK3), was no longer able to bind 14-3-3. Wild-type MARK3 was present in both the cytoplasm and plasma membrane, whereas the 17A-MARK3 mutant was strikingly localised at the plasma membrane. We provide data indicating that the membrane localisation of MARK3 required a highly conserved C-terminal domain, which has been termed kinase-associated domain-1 (KA-1). We also show that dissociation of 14-3-3 from MARK3 did not affect catalytic activity, and that a MARK3 mutant, which could not interact with 14-3-3, was normally active. Finally, we establish that there are significant differences in the subcellular localisation of MARK isoforms, as well as in the impact that atypical PKC overexpression has on 14-3-3 binding and localisation. Collectively, these results indicate that 14-3-3 binding to MARK isoforms is mediated by multiple phosphorylation sites, and serves to anchor MARK isoforms in the cytoplasm.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Göransson O,Deak M,Wullschleger S,Morrice NA,Prescott AR,Alessi DRdoi
10.1242/jcs.03097subject
Has Abstractpub_date
2006-10-01 00:00:00pages
4059-70issue
Pt 19eissn
0021-9533issn
1477-9137pii
jcs.03097journal_volume
119pub_type
杂志文章abstract::During the prometaphase stage of mitosis, the cell builds a bipolar spindle of microtubules that mechanically segregates sister chromatids between two daughter cells in anaphase. The spindle assembly checkpoint (SAC) is a quality control mechanism that monitors proper attachment of microtubules to chromosome kinetocho...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.191353
更新日期:2018-04-12 00:00:00
abstract::Endothelial permeability induced by thrombin and histamine is accompanied by actin stress fibre assembly and intercellular gap formation. Here, we investigate the roles of the Rho family GTPases Rho1, Rac1 and Cdc42 in regulating endothelial barrier function, and correlate this with their effects on F-actin organizati...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00
abstract::NADH:ubiquinone oxidoreductases catalyse the first step within the diverse pathways of mitochondrial NADH oxidation. In addition to the energy-conserving form commonly called complex I, fungi and plants contain much simpler alternative NADH:ubiquinone oxido-reductases that catalyze the same reaction but do not translo...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::Chick embryo fibroblasts cultivated in vitro and Ehrlich ascites tumor cells (in vivo or in vitro) have been treated with amphotericin B. Cell multiplication is strongly inhibited. Large clear zones appear in the fibroblast nucleoi (phase-contrast and electron-microscope observations). Many treated fibroblasts and tum...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1975-08-01 00:00:00
abstract::Postsynaptic density protein 95 (PSD-95/SAP-90) is a palmitoylated membrane-associated guanylate kinase that oligomerizes and clusters ion channels and associated signaling machinery at excitatory synapses in brain. However, the mechanism for PSD-95 oligomerization and its relationship to ion channel clustering remain...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.00617
更新日期:2003-08-01 00:00:00
abstract::In sciarid flies (Diptera, Sciaridae), one or two paternally derived X chromosomes are discarded from the soma at early cleavages to determine the sex of the embryo (XX, females; X0, males). X chromosome(s) elimination is achieved by an abnormal anaphase segregation so that X sister chromatids do not reach the poles a...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.128900
更新日期:2013-07-15 00:00:00
abstract::Autophagy is fundamental for cell and organismal health. Two types of autophagy are conserved in eukaryotes: macroautophagy and microautophagy. During macroautophagy, autophagosomes deliver cytoplasmic constituents to endosomes or lysosomes, whereas during microautophagy lytic organelles take up cytoplasm directly. Wh...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.246322
更新日期:2020-09-09 00:00:00
abstract::Syntaxin 1C (STX1C), produced by alternative splicing of the stx1A gene, is a soluble syntaxin lacking a SNARE domain and a transmembrane domain. It is unclear how soluble syntaxin can control intracellular membrane trafficking. We found that STX1C affected microtubule (MT) dynamics through its tubulin-binding domain ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.081943
更新日期:2012-02-15 00:00:00
abstract::Fatty acids constitute an important energy source for various tissues. The mechanisms that mediate and control uptake of free fatty acids from the circulation, however, are poorly understood. Here we show that efficient fatty-acid uptake by yeast cells requires the protein kinase Ypk1, the orthologue of the human seru...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.063073
更新日期:2010-07-01 00:00:00
abstract::MIP and MP70 are putative gap junction components in the plasma membranes of the mammalian lens fibre cells. We show now that MP70 can be solubilized separately from MIP in mild detergent solutions, and that this treatment results in the dissociation of the fibre gap junctions. Solubilized MP70 was isolated as 16.9 S ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1988-11-01 00:00:00
abstract::Stages of meiosis from the bluebell Endymion non-scriptus (L.) were studied by electron microscopy. The nucleolus went through the process of segregation at the beginning of meiosis with the movement to its surface of a pale-staining region. This region was shown to be the same as that called the 'L zone' or lacunae o...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1976-10-01 00:00:00
abstract::The production, transport, and disposition of material labelled with [3H]mannose were studied in microsurgically enucleated and control amoebae. Cells were injected with the precursor and samples were prepared for electron-microscope radioautography at intervals, up to 24 h later. Control cells showed heavy labelling ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1984-06-01 00:00:00
abstract::Host/symbiont specificity has been investigated in non-symbiotic and aposymbiotic brown and green hydra infected with various free-living and symbiotic species and strains of Chlorella and Chlorococcum. Morphology and ultrastructure of the symbioses obtained have been compared. Aposymbiotic Swiss Hydra viridis and Jap...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1986-12-01 00:00:00
abstract::Recently isolated trophoblasts express nitric oxide synthase 2 (NOS-2) and cyclooxygenase 2 (COX-2), decreasing the levels of the corresponding mRNAs when the cells were maintained in culture. The sustained expression of COX-2 and NOS-2 in trophoblasts was dependent on the activation of nuclear factor kappaB (NF-kappa...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::Mouse oocytes are induced by cytochalasin B to undergo 'pseudo-cleavage' in vitro into 2 equally sized and separable compartments. This response to the drug is dependent upon the meiotic state of the oocytes, as well as upon the presence of an intact zona pellucida. The resulting 2 cellular compartments can be complet...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1976-08-01 00:00:00
abstract::HSP27 and alphaB-crystallin are both members of the small heat shock protein family. alphaB-crystalllin has been proposed to modulate intermediate filaments and recently a mutation in alphaB-crystallin has been identified as the genetic basis of desmin related myopathy. This disease is characterised in its pathology b...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::Shape changes have been determined in human blood lymphocytes stimulated with OAG, diC8, PMA, colchicine or the hexapeptide fNLPNTL in short-term assays (30 min). Distinct types of shape-change responses were observed. Colchicine was active in generating a relatively small proportion of polarized lymphocytes (front-ta...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::Motile cilia generate directed hydrodynamic flow that is important for the motility of cells and extracellular fluids. To optimize directed hydrodynamic flow, motile cilia are organized and oriented into a polarized array. Basal bodies (BBs) nucleate and position motile cilia at the cell cortex. Cytoplasmic BB-associa...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.233726
更新日期:2019-08-07 00:00:00
abstract::Embryonal rhabdomyosarcomas (ERMSs) show elevated levels of PAX7, a transcription factor that marks quiescent adult muscle stem (satellite) cells and is important for proliferation and survival of activated satellite cells and whose timely repression is required for myogenic differentiation. However, the mechanism of ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.136259
更新日期:2014-04-15 00:00:00
abstract::Stem cell regeneration is crucial for both cell turnover and tissue healing in multicellular organisms. In Arabidopsis roots, a reduced group of cells known as the quiescent center (QC) act as a cell reservoir for surrounding stem cells during both normal growth and in response to external damage. Although cells of th...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.204065
更新日期:2018-01-29 00:00:00
abstract::Galectin-3 is a member of a closely related family of beta-galactoside-binding soluble proteins found in many vertebrate epithelial and myeloid cell types. The developmentally regulated presence of galectin-3 in tissues, for example kidney, and an affinity for many cell-surface and matrix glycoproteins indicate its im...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::The Wnt signal transduction pathway regulates various aspects of embryonal development and is involved in cancer formation. Wnts induce the stabilisation of cytosolic (beta)-catenin, which then associates with TCF transcription factors to regulate expression of Wnt-target genes. At various levels the Wnt pathway is su...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::Quantitative studies on the adhesive properties of transformed cells have yielded inconclusive and sometimes contradictory results. The present investigation has examined adhesive interactions between normal human fibroblasts, established as well as virus-transformed animal cell lines, and human tumour-derived cell li...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1978-10-01 00:00:00
abstract::Actin cytoskeleton self-organization in two cell types, fibroblasts and epitheliocytes, was studied in cells confined to isotropic adhesive islands. In fibroblasts plated onto islands of optimal size, an initially circular actin pattern evolves into a radial pattern of actin bundles that undergo asymmetric chiral swir...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.220780
更新日期:2019-03-07 00:00:00
abstract::We investigated the role of Pav-KLP, a kinesin-6, in the coordination of spindle and cortical dynamics during mitosis in Drosophila embryos. In vitro, Pav-KLP behaves as a dimer. In vivo, it localizes to mitotic spindles and furrows. Inhibition of Pav-KLP causes defects in both spindle dynamics and furrow ingression, ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.064048
更新日期:2010-06-01 00:00:00
abstract::Myofibrillar proteins assemble to form the highly ordered repetitive contractile structural unit known as a sarcomere. Studies of myogenesis in vertebrate cell culture and embryonic developmental systems have identified some of the processes involved during sarcomere formation. However, isoform changes during vertebra...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01024
更新日期:2004-04-01 00:00:00
abstract::Mammalian homologs of the Drosophila TRP protein have been shown to form cation-permeable channels in the plasma membrane but very little is known about the mechanisms that control their cell surface localization. Recently it has been demonstrated that the last three C-terminal amino acids (TRL) of TRPC4 comprise a PD...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract::We show that muscle satellite cells, traditionally considered as committed myogenic precursors, are comprised of Pax7-expressing progenitors that preserve a mesenchymal repertoire extending beyond a mere myogenic potential. Mouse satellite cells from freshly isolated single myofibers, cultured individually in serum-ri...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01419
更新日期:2004-10-15 00:00:00
abstract::Neurite outgrowth is known as a slow (days) process occurring in nerve cells and neurons during neurotrophin treatment and upon transfer to culture, respectively. Using Y27632, a drug that induces activation of Rac1, a downstream step of the neurotrophin signaling cascade, we have identified a new form of outgrowth, w...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.059634
更新日期:2010-01-15 00:00:00
abstract::The purpose of our studies was to determine the fate of different cell types present in early primary cultures of tracheal epithelial cells and, if possible, to elucidate the role they play in the establishment of the cultures. Epithelial cells were isolated from rat tracheas with 0.5% Pronase and were cultured on col...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00