Abstract:
:Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in development and human disease, including cancer. It is currently thought that the four-point one, ezrin, radixin, moesin (FERM)-kinase domain linker, which contains autophosphorylation site tyrosine (Y) 397, is not required for in vivo FAK function until late midgestation. Here, we directly tested this hypothesis by generating mice with FAK Y397-to-phenylalanine (F) mutations in the germline. We found that Y397F embryos exhibited reduced mesodermal fibronectin (FN) and osteopontin expression and died during mesoderm development akin to FAK kinase-dead mice. We identified myosin-1E (MYO1E), an actin-dependent molecular motor, to interact directly with the FAK FERM-kinase linker and induce FAK kinase activity and Y397 phosphorylation. Active FAK in turn accumulated in the nucleus where it led to the expression of osteopontin and other FN-type matrix in both mouse embryonic fibroblasts and human melanoma. Our data support a model in which FAK Y397 autophosphorylation is required for FAK function in vivo and is positively regulated by MYO1E.
journal_name
Proc Natl Acad Sci U S Aauthors
Heim JB,Squirewell EJ,Neu A,Zocher G,Sominidi-Damodaran S,Wyles SP,Nikolova E,Behrendt N,Saunte DM,Lock-Andersen J,Gaonkar KS,Yan H,Sarkaria JN,Krendel M,van Deursen J,Sprangers R,Stehle T,Böttcher RT,Lee JH,Ordog Tdoi
10.1073/pnas.1614894114subject
Has Abstractpub_date
2017-04-11 00:00:00pages
3933-3938issue
15eissn
0027-8424issn
1091-6490pii
1614894114journal_volume
114pub_type
杂志文章abstract::Identifying the drivers and processes that determine globally the geographic range size of species is crucial to understanding the geographic distribution of biodiversity and further predicting the response of species to current global changes. However, these drivers and processes are still poorly understood, and no 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.1902484116
更新日期:2019-07-02 00:00:00
abstract::The probability of choosing an alternative in a long sequence of repeated choices is proportional to the total reward derived from that alternative, a phenomenon known as Herrnstein's matching law. This behavior is remarkably conserved across species and experimental conditions, but its underlying neural mechanisms st...
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.0505220103
更新日期:2006-10-10 00:00:00
abstract::The foundation of marine coral reef ecosystems is calcium carbonate accumulated primarily by the action of hard corals (Coelenterata: Anthozoa: Scleractinia). Colonial hard coral polyps cover the surface of the reef and deposit calcium carbonate as the aragonite polymorph, stabilized into a continuous calcareous skele...
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.211439698
更新日期:2001-10-09 00:00:00
abstract::The thesis is developed that a low oxygen level Precambrian atmosphere presented early-evolving metazoan organisms with physiological connective tissue priorities resulting from the important molecular oxygen requirements in the biosynthesis of collagen hydroxyproline. Shells, cuticles, and carapaces which are not man...
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.65.4.781
更新日期:1970-04-01 00:00:00
abstract::The opportunistic pathogen Candida albicans can undergo phenotypic switching between a benign, unicellular phenotype and an invasive, multicellular form that causes candidiasis. Increasingly, strains of Candida are becoming resistant to antifungal drugs, making the treatment of candidiasis difficult, especially in imm...
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.0906145106
更新日期:2009-11-17 00:00:00
abstract::Recombination junctions of several Neurospora mitochondrial DNA (mtDNA) mutants and their revertants were identified. Their nucleotide sequences and putative secondary structures were determined in order to understand the nature of the elements involved in intramolecular recombination. Multiple deletions, involving th...
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.88.17.7684
更新日期:1991-09-01 00:00:00
abstract::Addition of a 0.5 M KCl wash fraction from rabbit reticulocyte ribosomes causes a 3- to 10-fold increase in the extent of translation of natural mRNAs by Krebs-cell lysates. In the presence of the wash fraction, 1 pmol of rabbit or mouse 10S RNA directs the incorporation of 80 pmol of leucine into rabbit globin. The a...
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.69.5.1299
更新日期:1972-05-01 00:00:00
abstract::If H denotes the classical Hilbert transform and Hu(x) = v(x), then the functions u(x) and v(x) are the values on the real axis of a pair of conjugate functions, harmonic in the upper half-plane. This note gives a generalization of the above concepts in which the Laplace equation Deltau = 0 is replaced by the Yukawa 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.69.12.3677
更新日期:1972-12-01 00:00:00
abstract::Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse muta...
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.112212199
更新日期:2002-05-28 00:00:00
abstract::Filamentous actin (F-actin) cytoskeletal remodeling is critical for glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells, and its dysregulation causes type 2 diabetes. The adaptor protein APPL1 promotes first-phase GSIS by up-regulating soluble N-ethylmaleimide-sensitive factor attachment protein receptor...
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.2016997117
更新日期:2020-11-10 00:00:00
abstract::From a flounder pituitary cDNA library, cDNA clones encoding a 28-kDa glycoprotein produced by the pars intermedia of the pituitary were isolated and characterized. Nucleotide sequencing demonstrated a precursor of the 28-kDa protein, which consisted of 231 amino acid residues, to be cleaved into a signal peptide (24 ...
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.87.11.4330
更新日期:1990-06-01 00:00:00
abstract::Molecular weights of the isolated proteins from the 30S and 50S ribosomal subunits of Escherichia coli were determined by two independent methods: polyacrylamide gel electrophoresis with sodium dodecylsulphate and equilibrium sedimentation. The values for the molecular weights determined by gel electrophoresis range f...
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.67.4.1909
更新日期:1970-12-01 00:00:00
abstract::We describe a method based on a phagemid vector with helper phage rescue for the construction and rapid analysis of combinatorial antibody Fab libraries. This approach should allow the generation and selection of many monoclonal antibodies. Antibody genes are expressed in concert with phage morphogenesis, thereby allo...
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.88.10.4363
更新日期:1991-05-15 00:00:00
abstract::Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. ...
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.1410776112
更新日期:2015-02-17 00:00:00
abstract::Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically syn...
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.1210483109
更新日期:2012-09-11 00:00:00
abstract::The trilaminate vascular architecture provides biochemical regulation and mechanical integrity. Yet regulatory control can be regained after injury without recapitulating tertiary structure. Tissue-engineered (TE) endothelium controls repair even when placed in the perivascular space of injured vessels. It remains unc...
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.0802463105
更新日期:2008-05-13 00:00:00
abstract::The emerging method of femtosecond crystallography (FX) may extend the diffraction resolution accessible from small radiation-sensitive crystals and provides a means to determine catalytically accurate structures of acutely radiation-sensitive metalloenzymes. Automated goniometer-based instrumentation developed for us...
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.1418733111
更新日期:2014-12-02 00:00:00
abstract::We investigate energy transport through an alpha-aminoisobutyric acid-based 3(10)-helix dissolved in chloroform in a combined experimental-theoretical approach. Vibrational energy is locally deposited at the N terminus of the helix by ultrafast internal conversion of a covalently attached, electronically excited, azob...
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.0701762104
更新日期:2007-07-31 00:00:00
abstract::Infection by Plasmodium, the causative agent of malaria, is associated with hemolysis and therefore with release of hemoglobin from RBC. Under inflammatory conditions, cell-free hemoglobin can be oxidized, releasing its heme prosthetic groups and producing deleterious free heme. Here we demonstrate that survival of a ...
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.0903419106
更新日期:2009-09-15 00:00:00
abstract::Glutamine synthetase (GS) is expressed in the neural retina only in Muller glia cells and is inducible with cortisol. A chicken genomic clone that contains at least part of the coding region for the GS enzyme was used to investigate developmental changes in the level of GS mRNA in embryonic chicken retina. A major GS ...
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.83.23.9060
更新日期:1986-12-01 00:00:00
abstract::Treatment of lymphocytes with inducers of interferon alpha (IFN-alpha) results in the production of corticotropin (ACTH) and endorphin-like activities. The pro-opiomelanocortin-derived hormones ACTH and alpha-, beta-, and gamma-endorphin and the structurally related hormones [Leu]- and [Met]enkephalin were therefore t...
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.79.13.4171
更新日期:1982-07-01 00:00:00
abstract::The mouse genes encoding the constitutively expressed complement component C4 and its closely related isoform C4-Slp (sex-limited protein), which is expressed only in male animals of several strains, provide a unique model to study sequence elements and trans-acting factors responsible for androgen responsiveness. Our...
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.95.15.8750
更新日期:1998-07-21 00:00:00
abstract::Caseinolytic proteases (ClpPs) are large oligomeric protein complexes that contribute to cell homeostasis as well as virulence regulation in bacteria. Although most organisms possess a single ClpP protein, some organisms encode two or more ClpP isoforms. Here, we elucidated the crystal structures of ClpP1 and ClpP2 fr...
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.1219125110
更新日期:2013-07-09 00:00:00
abstract::Retinal prosthetics offer hope for patients with retinal degenerative diseases. There are 20-25 million people worldwide who are blind or facing blindness due to these diseases, and they have few treatment options. Drug therapies are able to help a small fraction of the population, but for the vast majority, their bes...
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.1207035109
更新日期:2012-09-11 00:00:00
abstract::The activation of additional promoter sites by production of an alternative sigma subunit for RNA polymerase is a common strategy for the coordinate regulation of gene expression. Many alternative sigma factors control genes for specialized, and often narrowly distributed, functions. For example, most of the alternati...
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.89.11.5123
更新日期:1992-06-01 00:00:00
abstract::The proton-translocating subunit of wheat chloroplast ATP synthase is encoded by a chloroplast gene that has been accurately mapped and whose nucleotide sequence has been determined. The predicted sequence of 81 amino acids has been confirmed in part by determination of the sequence of the first 40 amino acids from th...
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.79.22.6903
更新日期:1982-11-01 00:00:00
abstract::Bacteriorhodopsin from Halobacterium halobium has been solubilized in the nonionic detergent Triton X-100. The circular dichroic spectrum and hydrodynamic properties indicate that the structure of this protein in the detergent is not significantly altered from that of the native membrane-bound form. Bacteriorhodopsin ...
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.74.7.2803
更新日期:1977-07-01 00:00:00
abstract::We have initiated immunological and drug-binding studies on the tubulins from different higher plant species. Antibodies were raised against electrophoretically separated rose (Rosa sp.) tubulin alpha- and beta-subunits and characterized by immunoblot autoradiographic assays. Each IgG preparation bound to its antigen ...
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.81.5.1440
更新日期:1984-03-01 00:00:00
abstract::CD4+ T cells recognize major histocompatibility complex (MHC) class II-bound peptides that are primarily obtained from extracellular sources. Endogenously synthesized proteins that readily enter the MHC class I presentation pathway are generally excluded from the MHC class II presentation pathway. We show here that 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.92.16.7217
更新日期:1995-08-01 00:00:00
abstract::While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based ...
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.1504447112
更新日期:2015-07-14 00:00:00