RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility.

Abstract:

:p90 ribosomal S6 kinase (RSK1) is an effector of both Ras/MEK/MAPK and PI3K/PDK1 pathways. We present evidence that RSK1 drives p27 phosphorylation at T198 to increase RhoA-p27 binding and cell motility. RSK1 activation and p27pT198 both increase in early G(1). As for many kinase-substrate pairs, cellular RSK1 coprecipitates with p27. siRNA to RSK1 and RSK1 inhibition both rapidly reduce cellular p27pT198. RSK1 overexpression increases p27pT198, p27-cyclin D1-Cdk4 complexes, and p27 stability. Moreover, RSK1 transfectants show mislocalization of p27 to cytoplasm, increased motility, and reduced RhoA-GTP, phospho-cofilin, and actin stress fibers, all of which were reversed by shRNA to p27. Phosphorylation by RSK1 increased p27pT198 binding to RhoA in vitro, whereas p27T157A/T198A bound poorly to RhoA compared with WTp27 in cells. Coprecipitation of cellular p27-RhoA was increased in cells with constitutive PI3K activation and increased in early G(1). Thus T198 phosphorylation not only stabilizes p27 and mislocalizes p27 to the cytoplasm but also promotes RhoA-p27 interaction and RhoA pathway inhibition. These data link p27 phosphorylation at T198 and cell motility. As for other PI3K effectors, RSK1 phosphorylates p27 at T198. Because RSK1 is also activated by MAPK, the increased cell motility and metastatic potential of cancer cells with PI3K and/or MAPK pathway activation may result in part from RSK1 activation, leading to accumulation of p27T198 in the cytoplasm, p27:RhoA binding, inhibition of RhoA/Rock pathway activation, and loss of actomyosin stability.

authors

Larrea MD,Hong F,Wander SA,da Silva TG,Helfman D,Lannigan D,Smith JA,Slingerland JM

doi

10.1073/pnas.0805057106

subject

Has Abstract

pub_date

2009-06-09 00:00:00

pages

9268-73

issue

23

eissn

0027-8424

issn

1091-6490

pii

0805057106

journal_volume

106

pub_type

杂志文章
  • Visualizing synaptic vesicle turnover and pool refilling driven by calcium nanodomains at presynaptic active zones of ribbon synapses.

    abstract::Ribbon synapses of photoreceptor cells and second-order bipolar neurons in the retina are specialized to transmit graded signals that encode light intensity. Neurotransmitter release at ribbon synapses exhibits two kinetically distinct components, which serve different sensory functions. The faster component is deplet...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1323962111

    authors: Vaithianathan T,Matthews G

    更新日期:2014-06-10 00:00:00

  • The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells.

    abstract::Ectopic activation of the Wnt signaling pathway is highly oncogenic for many human tissues. Here, we show that ectopic Wnt signaling increases the effective stem cell activity in mouse mammary glands in vivo. Furthermore, Wnt effectors induce the accumulation of mouse mammary epithelial progenitors (assayed by Hoechst...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0400699101

    authors: Liu BY,McDermott SP,Khwaja SS,Alexander CM

    更新日期:2004-03-23 00:00:00

  • Engineering graded tissue interfaces.

    abstract::Interfacial zones between tissues provide specialized, transitional junctions central to normal tissue function. Regenerative medicine strategies focused on multiple cell types and/or bi/tri-layered scaffolds do not provide continuously graded interfaces, severely limiting the integration and biological performance of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0801988105

    authors: Phillips JE,Burns KL,Le Doux JM,Guldberg RE,García AJ

    更新日期:2008-08-26 00:00:00

  • Photolabeling evidence for calcium-induced conformational changes at the ATP binding site of scallop myosin.

    abstract::A change in the conformation of the active site of scallop myosin under the influence of regulatory amounts of Ca2+ has been identified by use of the ADP photoaffinity analog 2-[(4-azido-2-nitrophenyl)amino]ethyl diphosphate (NANDP). NANDP, trapped at the active site with Mn2+ and vanadate, photolabeled preferentially...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.1.35

    authors: Kerwin BA,Yount RG

    更新日期:1993-01-01 00:00:00

  • Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes.

    abstract::Cyclophilins are a family of proteins that bind cyclosporin A (CsA) and possess peptidyl-prolyl cis-trans isomerase activity. In addition, they are secreted by activated cells and act in a cytokine-like manner, presumably via signaling through a cell surface cyclophilin receptor. More recently, host-derived cyclophili...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.4.1758

    authors: Sherry B,Zybarth G,Alfano M,Dubrovsky L,Mitchell R,Rich D,Ulrich P,Bucala R,Cerami A,Bukrinsky M

    更新日期:1998-02-17 00:00:00

  • Cultured aortic endothelial cells from pigs with von Willebrand disease: in vitro model for studying the molecular defect(s) of the disease.

    abstract::Aortic endothelial cells from normal pigs and pigs with von Willebrand disease have been established in long-term cultures. Both cultures appeared similar in terms of general growth characteristics, morphologic features and ultrastructure. Immunofluorescent staining of these cultures with chicken (or rabbit) antiporci...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.74.12.5702

    authors: Booyse FM,Quarfoot AJ,Bell S,Fass DN,Lewis JC,Mann KG,Bowie EJ

    更新日期:1977-12-01 00:00:00

  • Messages diffuse faster than messengers.

    abstract::In many cell-signaling pathways, information is transmitted by the diffusion of messenger molecules. Diffusion coefficients characterize the messenger's spatial range and the characteristic times of signal propagation. Inside cells, particles usually diffuse in the presence of immobile binding sites (or traps). It is ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0509576103

    authors: Pando B,Dawson SP,Mak DO,Pearson JE

    更新日期:2006-04-04 00:00:00

  • Epac signaling is required for hippocampus-dependent memory retrieval.

    abstract::Previously we uncovered a critical role for norepinephrine and beta(1)-adrenergic signaling in hippocampus-dependent memory retrieval. Because the beta(1) receptor couples to G(s), we examine here whether cAMP is also required for contextual memory retrieval. Using pharmacologic and genetic approaches to manipulate cA...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0804172105

    authors: Ouyang M,Zhang L,Zhu JJ,Schwede F,Thomas SA

    更新日期:2008-08-19 00:00:00

  • Fusion protein Isl1-Lhx3 specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs.

    abstract::Combinatorial transcription codes generate the myriad of cell types during development and thus likely provide crucial insights into directed differentiation of stem cells to a specific cell type. The LIM complex composed of Isl1 and Lhx3 directs the specification of spinal motor neurons (MNs) in embryos. Here, we rep...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1114515109

    authors: Lee S,Cuvillier JM,Lee B,Shen R,Lee JW,Lee SK

    更新日期:2012-02-28 00:00:00

  • A dominant positive and negative selectable gene for use in mammalian cells.

    abstract::We have constructed three different fusion genes containing the herpes simplex virus thymidine kinase (HSV tk) and the bacterial neomycin phosphotransferase (neo) genes. All three fusion genes utilize the HSV tk promoter but differ at the junction of their components. We have determined if the fusion genes are bifunct...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.23.10416

    authors: Schwartz F,Maeda N,Smithies O,Hickey R,Edelmann W,Skoultchi A,Kucherlapati R

    更新日期:1991-12-01 00:00:00

  • Muscle-regulated expression and determinants for neuromuscular junctional localization of the mouse RIalpha regulatory subunit of cAMP-dependent protein kinase.

    abstract::In skeletal muscle, transcription of the gene encoding the mouse type Ialpha (RIalpha) subunit of the cAMP-dependent protein kinase is initiated from the alternative noncoding first exons 1a and 1b. Here, we report that activity of the promoter upstream of exon 1a (Pa) depends on two adjacent E boxes (E1 and E2) in NI...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.081393598

    authors: Barradeau S,Imaizumi-Scherrer T,Weiss MC,Faust DM

    更新日期:2001-04-24 00:00:00

  • Biological and serological characterization of radiation leukemia virus.

    abstract::Radiation leukemia virus, isolated from radiation-induced lymphomas in C57BL/Ka mice and propagated in that strain, is thymotropic and leukemogenic in vivo but replicates poorly, if at all, in mouse and mink fibroblast cultures in vitro. Comparative studies indicate that this naturally occurring virus is distinct from...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.73.12.4675

    authors: Declève A,Lieberman M,Ihle JN,Kaplan HS

    更新日期:1976-12-01 00:00:00

  • The choroid plexus epithelium is the site of the organic anion transport protein in the brain.

    abstract::The mRNA for organic anion transport protein (oatp) was previously shown to be present in abundance in liver and kidney, and in small amounts in brain. Data obtained from experiments with reverse transcriptase-PCR techniques and in situ hybridization analysis showed that the oatp mRNA is present within the brain, loca...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.1.283

    authors: Angeletti RH,Novikoff PM,Juvvadi SR,Fritschy JM,Meier PJ,Wolkoff AW

    更新日期:1997-01-07 00:00:00

  • Defects in inositol 1,4,5-trisphosphate receptor expression, Ca(2+) signaling, and insulin secretion in the anx7(+/-) knockout mouse.

    abstract::The mammalian anx7 gene codes for a Ca(2+)-activated GTPase, which supports Ca(2+)/GTP-dependent secretion events and Ca(2+) channel activities in vitro and in vivo. To test whether anx7 might be involved in Ca(2+) signaling in secreting pancreatic beta cells, we knocked out the anx7 gene in the mouse and tested the i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.24.13783

    authors: Srivastava M,Atwater I,Glasman M,Leighton X,Goping G,Caohuy H,Miller G,Pichel J,Westphal H,Mears D,Rojas E,Pollard HB

    更新日期:1999-11-23 00:00:00

  • The N-terminal domain of PsaF: precise recognition site for binding and fast electron transfer from cytochrome c6 and plastocyanin to photosystem I of Chlamydomonas reinhardtii.

    abstract::The PsaF-deficient mutant 3bF of Chlamydomonas reinhardtii was used to modify PsaF by nuclear transformation and site-directed mutagenesis. Four lysine residues in the N-terminal domain of PsaF, which have been postulated to form the positively charged face of a putative amphipathic alpha-helical structure were altere...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.13.7339

    authors: Hippler M,Drepper F,Haehnel W,Rochaix JD

    更新日期:1998-06-23 00:00:00

  • Activation of the pp90rsk and mitogen-activated serine/threonine protein kinases by ionizing radiation.

    abstract::The cellular response to ionizing radiation (IR) includes induction of the c-jun and EGR1 early response genes. The present work has examined potential cytoplasmic signaling cascades that transduce IR-induced signals to the nucleus. The results demonstrate activation of the 40S ribosomal protein S6 kinase, pp90rsk, in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.12.5416

    authors: Kharbanda S,Saleem A,Shafman T,Emoto Y,Weichselbaum R,Kufe D

    更新日期:1994-06-07 00:00:00

  • Nucleotide binding-promoted conformational changes release a nonnative polypeptide from the Escherichia coli chaperonin GroEL.

    abstract::The Escherichia coli chaperonins GroEL and GroES facilitate the refolding of polypeptide chains in an ATP hydrolysis-dependent reaction. The elementary steps in the binding and release of polypeptide substrates to GroEL were investigated in surface plasmon resonance studies to measure the rates of binding and dissocia...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.5.1977

    authors: Lin Z,Eisenstein E

    更新日期:1996-03-05 00:00:00

  • Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cells.

    abstract::T cells interacting with antigen-presenting cells (APCs) form an "immunological synapse" (IS), a bull's-eye pattern composed of a central supramolecular activation cluster enriched with T cell receptors (TCRs) surrounded by a ring of adhesion molecules (a peripheral supramolecular activation cluster). The mechanism re...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0710258105

    authors: Kaizuka Y,Douglass AD,Varma R,Dustin ML,Vale RD

    更新日期:2007-12-18 00:00:00

  • Tropical forests can maintain hyperdiversity because of enemies.

    abstract::Explaining the maintenance of tropical forest diversity under the countervailing forces of drift and competition poses a major challenge to ecological theory. Janzen-Connell effects, in which host-specific natural enemies restrict the recruitment of juveniles near conspecific adults, provide a potential mechanism. Jan...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1813211116

    authors: Levi T,Barfield M,Barrantes S,Sullivan C,Holt RD,Terborgh J

    更新日期:2019-01-08 00:00:00

  • Cell-specific differences in the requirements for translation quality control.

    abstract::Protein synthesis has an overall error rate of approximately 10(-4) for each mRNA codon translated. The fidelity of translation is mainly determined by two events: synthesis of cognate amino acid:tRNA pairs by aminoacyl-tRNA synthetases (aaRSs) and accurate selection of aminoacyl-tRNAs (aa-tRNAs) by the ribosome. To e...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0909640107

    authors: Reynolds NM,Ling J,Roy H,Banerjee R,Repasky SE,Hamel P,Ibba M

    更新日期:2010-03-02 00:00:00

  • The MCK mouse heart model of Friedreich's ataxia: Alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation.

    abstract::There is no effective treatment for the cardiomyopathy of the most common autosomal recessive ataxia, Friedreich's ataxia (FA). The identification of potentially toxic mitochondrial (MIT) iron (Fe) deposits in FA suggests that Fe plays a role in its pathogenesis. This study used the muscle creatine kinase conditional ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0804261105

    authors: Whitnall M,Suryo Rahmanto Y,Sutak R,Xu X,Becker EM,Mikhael MR,Ponka P,Richardson DR

    更新日期:2008-07-15 00:00:00

  • Coevolution of cultural intelligence, extended life history, sociality, and brain size in primates.

    abstract::Explanations for primate brain expansion and the evolution of human cognition and culture remain contentious despite extensive research. While multiple comparative analyses have investigated variation in brain size across primate species, very few have addressed why primates vary in how much they use social learning. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1620734114

    authors: Street SE,Navarrete AF,Reader SM,Laland KN

    更新日期:2017-07-25 00:00:00

  • Organ boundary1 defines a gene expressed at the junction between the shoot apical meristem and lateral organs.

    abstract::We identify a gene, organ boundary1 (OBO1), by its unique pattern of enhancer- driven GFP expression at the boundaries between the apical meristems and lateral organs in Arabidopsis embryos, seedlings, and mature plants. OBO1 also is expressed at the root apical meristem and in distinct cell files surrounding this are...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1018542108

    authors: Cho E,Zambryski PC

    更新日期:2011-02-01 00:00:00

  • Propagating conformational changes over long (and short) distances in proteins.

    abstract::The problem of the propagation of conformational changes over long distances or through a closely packed protein is shown to fit a model of a ligand-induced conformational change between two protein states selected by evolution. Moreover, the kinetics of the pathway between these states is also selected so that the en...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.161239298

    authors: Yu EW,Koshland DE Jr

    更新日期:2001-08-14 00:00:00

  • Differential global structural changes in the core particle of yeast and mouse proteasome induced by ligand binding.

    abstract::Two clusters of configurations of the main proteolytic subunit β5 were identified by principal component analysis of crystal structures of the yeast proteasome core particle (yCP). The apo-cluster encompasses unliganded species and complexes with nonpeptidic ligands, and the pep-cluster comprises complexes with peptid...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1408018111

    authors: Arciniega M,Beck P,Lange OF,Groll M,Huber R

    更新日期:2014-07-01 00:00:00

  • Transport of sodium, chloride, and taurocholate by cultured rat hepatocytes.

    abstract::Transport of sodium, chloride, and taurocholate was studied in primary cultures of adult rat hepatocytes incubated in a balanced electrolyte solution containing 150 mM NaCl, various concentrations of taurocholate, and (22)Na, (36)Cl, [(3)H]taurocholate, and 3-O-[(3)H]methyl-D-glucose. Lithium chloride, choline chlorid...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.2.986

    authors: Scharschmidt BF,Stephens JE

    更新日期:1981-02-01 00:00:00

  • Yeast hormone response element assays detect and characterize GRIP1 coactivator-dependent activation of transcription by thyroid and retinoid nuclear receptors.

    abstract::The mouse glucocorticoid receptor-interacting protein (GRIP1) is a member of the ERAP160 family of nuclear receptor (NR) coactivators (including SRC-1 and TIF2) which function as bridging proteins between ligand-activated NRs bound to cognate hormone-response elements (HREs) and the transcription initiation apparatus ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.8.3697

    authors: Walfish PG,Yoganathan T,Yang YF,Hong H,Butt TR,Stallcup MR

    更新日期:1997-04-15 00:00:00

  • Elongation of displacement-loop strands in human and mouse mitochondrial DNA is arrested near specific template sequences.

    abstract::Animal mitochondrial DNA (mtDNA) maintains a displacement loop (D loop) at the heavy strand origin of replication. These D loops represent sharply limited synthesis of heavy strands and provide a unique opportunity to examine the termination of DNA synthesis. Direct sizing at the nucleotide level indicates that the 3'...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.10.6116

    authors: Doda JN,Wright CT,Clayton DA

    更新日期:1981-10-01 00:00:00

  • Genome-sized RNA from reovirus particles.

    abstract::Spider-like forms of purified reovirus RNA have been characterized by electron microscopy. These structures contained 11.3 +/- 0.8 mum of double-stranded RNA and up to 20 arms, each of distinct length. Length measurements of 64 "spiders" suggest that in these structures the viral genome is folded fairly specifically. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.11.4317

    authors: Kavenoff R,Talcove D,Mudd JA

    更新日期:1975-11-01 00:00:00

  • CytA enables CryIV endotoxins of Bacillus thuringiensis to overcome high levels of CryIV resistance in the mosquito, Culex quinquefasciatus.

    abstract::Cry proteins produced by Bacillus thuringiensis are selective biodegradable insecticides used increasingly in bacterial insecticides and transgenic plants as alternatives to synthetic chemical insecticides. However, the potential for development of resistance and cross-resistance in target insect populations to Cry pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.20.10536

    authors: Wirth MC,Georghiou GP,Federici BA

    更新日期:1997-09-30 00:00:00