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Role of Rac1 and oxygen radicals in collagenase-1 expression induced by cell shape change (1998)

F. Kheradmand ; E. Werner ; P. Tremble ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 280(5365): 898-902.

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Publication Date: 1998-05-23

Description: Integrin-mediated reorganization of cell shape leads to an altered cellular phenotype. Disruption of the actin cytoskeleton, initiated by binding of soluble antibody to alpha5beta1 integrin, led to increased expression of the collagenase-1 gene in rabbit synovial fibroblasts. Activation of the guanosine triphosphate-binding protein Rac1, which was downstream of the integrin, was necessary for this process, and expression of activated Rac1 was sufficient to increase expression of collagenase-1. Rac1 activation generated reactive oxygen species that were essential for nuclear factor kappa B-dependent transcriptional regulation of interleukin-1alpha, which, in an autocrine manner, induced collagenase-1 gene expression. Remodeling of the extracellular matrix and consequent alterations of integrin-mediated adhesion and cytoarchitecture are central to development, wound healing, inflammation, and malignant disease. The resulting activation of Rac1 may lead to altered gene regulation and alterations in cellular morphogenesis, migration, and invasion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kheradmand, F -- Werner, E -- Tremble, P -- Symons, M -- Werb, Z -- AR20684/AR/NIAMS NIH HHS/ -- DE10306/DE/NIDCR NIH HHS/ -- HL03732/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 May 8;280(5365):898-902.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California, San Francisco, CA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9572733" target="_blank"〉PubMed〈/a〉

Keywords: Animals ; Cell Line ; *Cell Size ; Collagenases/*genetics ; Cytochalasin D/pharmacology ; Enzyme Activation ; Fibroblasts ; Free Radicals ; GTP Phosphohydrolases/genetics/*metabolism ; GTP-Binding Proteins/genetics/*metabolism ; *Gene Expression Regulation, Enzymologic ; Genes, Reporter ; Hydrogen Peroxide ; Interleukin-1/genetics/metabolism ; Matrix Metalloproteinase 1 ; NF-kappa B/metabolism ; Rabbits ; Reactive Oxygen Species/*metabolism ; Receptors, Fibronectin/physiology ; Transcription, Genetic ; rac GTP-Binding Proteins

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

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Binding of 14-3-3 proteins to the protein kinase Raf and effects on its activation (1994)

E. Freed ; M. Symons ; S. G. Macdonald ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 265(5179): 1713-6.

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Publication Date: 1994-09-16

Description: To identify proteins that may participate in the activation of the protein kinase Raf, proteins that interact with Raf were selected in a two-hybrid screen. Two members of the 14-3-3 protein family were isolated that interacted with both the amino terminal regulatory regions of Raf and the kinase domain of Raf, but did not compete with the guanine nucleotide-binding protein Ras for binding to Raf. 14-3-3 proteins associated with Raf in mammalian cells and accompanied Raf to the membrane in the presence of activated Ras. In yeast cells expressing Raf and MEK, mammalian 14-3-3 beta or 14-3-3 zeta activated Raf to a similar extent as did expression of Ras. Therefore, 14-3-3 proteins may participate in or be required for the regulation of Raf function. These findings suggest a role for 14-3-3 proteins in Raf-mediated signal transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freed, E -- Symons, M -- Macdonald, S G -- McCormick, F -- Ruggieri, R -- New York, N.Y. -- Science. 1994 Sep 16;265(5179):1713-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Onyx Pharmaceuticals, Richmond, CA 94806-5206.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8085158" target="_blank"〉PubMed〈/a〉

Keywords: 14-3-3 Proteins ; Amino Acid Sequence ; Animals ; Cell Line ; Cell Membrane/enzymology ; Cytosol/enzymology ; Enzyme Activation ; GTP-Binding Proteins/metabolism ; HeLa Cells ; Humans ; MAP Kinase Kinase 1 ; *Mitogen-Activated Protein Kinase Kinases ; Molecular Sequence Data ; Nerve Tissue Proteins/*metabolism ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Protein-Tyrosine Kinases/genetics/metabolism ; Proto-Oncogene Proteins/chemistry/*metabolism ; Proto-Oncogene Proteins c-raf ; Recombinant Proteins/metabolism ; Saccharomyces cerevisiae/genetics/growth & development ; Signal Transduction ; *Tyrosine 3-Monooxygenase ; Zinc Fingers

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

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Activation of Raf as a result of recruitment to the plasma membrane (1994)

D. Stokoe ; S. G. Macdonald ; K. Cadwallader ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 264(5164): 1463-7.

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Publication Date: 1994-06-03

Description: The small guanine nucleotide binding protein Ras participates in a growth promoting signal transduction pathway. The mechanism by which interaction of Ras with the protein kinase Raf leads to activation of Raf was studied. Raf was targeted to the plasma membrane by addition of the COOH-terminal localization signals of K-ras. This modified form of Raf (RafCAAX) was activated to the same extent as Raf coexpressed with oncogenic mutant Ras. Plasma membrane localization rather than farnesylation or the presence of the additional COOH-terminal sequence accounted for the activation of RafCAAX. The activation of RafCAAX was completely independent of Ras; it was neither potentiated by oncogenic mutant Ras nor abrogated by dominant negative Ras. Raf, once recruited to the plasma membrane, was not anchored there by Ras; most activated Raf in cells was associated with plasma membrane cytoskeletal elements, not the lipid bilayer. Thus, Ras functions in the activation of Raf by recruiting Raf to the plasma membrane where a separate, Ras-independent, activation of Raf occurs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokoe, D -- Macdonald, S G -- Cadwallader, K -- Symons, M -- Hancock, J F -- New York, N.Y. -- Science. 1994 Jun 3;264(5164):1463-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ONXY Pharmaceuticals, Richmond, CA 94806.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7811320" target="_blank"〉PubMed〈/a〉

Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Cell Membrane/*enzymology ; Cytosol/enzymology ; Enzyme Activation ; GTP-Binding Proteins/*metabolism ; MAP Kinase Kinase 1 ; Mitogen-Activated Protein Kinase 1 ; *Mitogen-Activated Protein Kinase Kinases ; Models, Biological ; Molecular Sequence Data ; Protein-Serine-Threonine Kinases/chemistry/*metabolism ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins/chemistry/*metabolism ; Proto-Oncogene Proteins c-raf ; Recombinant Fusion Proteins/metabolism

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

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Uniqueness from discrete data in an inverse spectral problem for a pencil of ordinary differential operators (2016)

Brown, M., Marletta, M., Symons, F.

Oxford University Press

In: Journal of the London Mathematical Society

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Publication Date: 2016-12-22

Description: We prove a pair of uniqueness theorems for an inverse problem for an ordinary differential operator pencil of second order. The uniqueness is achieved from a discrete set of data, namely, the values at the points $-n^2\ (n\in \mathbb {N})$ of (a physically appropriate generalization of) the Weyl–Titchmarsh $m$ -function $m(\lambda )$ for the problem. As a corollary, we establish a uniqueness result for a physically motivated inverse problem inspired by Berry and Dennis (‘Boundary-condition-varying circle billiards and gratings: the Dirichlet singularity’, J. Phys. A: Math. Theor. 41 (2008) 135203). To achieve these results, we prove a limit-circle analogue to the limit-point $m$ -function interpolation result of Rybkin and Tuan (‘A new interpolation formula for the Titchmarsh–Weyl $m$ -function’, Proc. Amer. Math. Soc. 137 (2009) 4177–4185); however, our proof, using a Mittag-Leffler series representation of $m(\lambda )$ , involves a rather different method from theirs, circumventing the $A$ -amplitude representation of Simon (‘A new approach to inverse spectral theory, I. Fundamental formalism’, Ann. Math. $(2)$ 150 (1999) 1029–1057). Uniqueness of the potential then follows by appeal to a Borg–Marčenko argument.

Print ISSN: 0024-6107

Electronic ISSN: 1469-7750

Topics: Mathematics

Published by Oxford University Press

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Uniqueness from discrete data in an inverse spectral problem for a pencil of ordinary differential operators (2018)

Brown M, Marletta M, Symons F.

Oxford University Press

In: Journal of the London Mathematical Society

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Publication Date: 2018-03-06

Description: We prove a pair of uniqueness theorems for an inverse problem for an ordinary differential operator pencil of second order. The uniqueness is achieved from a discrete set of data, namely, the values at the points $-n^2\ (n\in \mathbb {N})$ of (a physically appropriate generalization of) the Weyl–Titchmarsh $m$-function $m(\lambda )$ for the problem. As a corollary, we establish a uniqueness result for a physically motivated inverse problem inspired by Berry and Dennis (‘Boundary-condition-varying circle billiards and gratings: the Dirichlet singularity’, J. Phys. A: Math. Theor. 41 (2008) 135203).To achieve these results, we prove a limit-circle analogue to the limit-point $m$-function interpolation result of Rybkin and Tuan (‘A new interpolation formula for the Titchmarsh–Weyl $m$-function’, Proc. Amer. Math. Soc. 137 (2009) 4177–4185); however, our proof, using a Mittag-Leffler series representation of $m(\lambda )$, involves a rather different method from theirs, circumventing the $A$-amplitude representation of Simon (‘A new approach to inverse spectral theory, I. Fundamental formalism’, Ann. Math. $(2)$ 150 (1999) 1029–1057). Uniqueness of the potential then follows by appeal to a Borg–Marčenko argument.

Print ISSN: 0024-6107

Electronic ISSN: 1469-7750

Topics: Mathematics

Published by Oxford University Press

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