scholarly journals Fibroblast Growth Factor Receptor 2 Phosphorylation on Serine 779 Couples to 14-3-3 and Regulates Cell Survival and Proliferation

2008 ◽  
Vol 28 (10) ◽  
pp. 3372-3385 ◽  
Author(s):  
Ana Lonic ◽  
Emma F. Barry ◽  
Cindy Quach ◽  
Bostjan Kobe ◽  
Neil Saunders ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Survival ◽  
Intracellular Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Cell Surface Receptors ◽  
Specific Cell ◽  
Fibroblast Growth ◽  
Surface Receptors ◽  
Biological Responses ◽  
Cell Survival And Proliferation

ABSTRACT The fibroblast growth factors (FGFs) exert their diverse (or pleiotropic) biological responses through the binding and activation of specific cell surface receptors (FGFRs). While FGFRs are known to initiate intracellular signaling through receptor tyrosine phosphorylation, the precise mechanisms by which the FGFRs regulate pleiotropic biological responses remain unclear. We now identify a new mechanism by which FGFR2 is able to regulate intracellular signaling and cellular responses. We show that FGFR2 is phosphorylated on serine 779 (S779) in response to FGF2. S779, which lies adjacent to the phospholipase Cγ binding site at Y766, provides a docking site for the 14-3-3 phosphoserine-binding proteins and is essential for the full activation of the phosphatidylinositol 3-kinase and Ras/mitogen-activated protein kinase pathways. Furthermore, S779 signaling is essential for promoting cell survival and proliferation in both Ba/F3 cells and BALB/c 3T3 fibroblasts. This new mode of FGFR2 phosphoserine signaling via the 14-3-3 proteins may provide an increased repertoire of signaling outputs to allow the regulation of pleiotropic biological responses. In this regard, we have identified conserved putative phosphotyrosine/phosphoserine motifs in the cytoplasmic domains of diverse cell surface receptors, suggesting that they may perform important functional roles beyond the FGFRs.

Quantitation of alpha-factor internalization and response during the Saccharomyces cerevisiae cell cycle

1991 ◽  
Vol 11 (10) ◽  
pp. 5251-5258
Author(s):  
B Zanolari ◽  
H Riezman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Surface ◽  
Cell Surface Receptors ◽  
Specific Cell ◽  
Surface Receptors ◽  
Cycle Arrest ◽  
A Cells ◽  
Alpha Factor ◽  
Inducible Genes

The alpha-factor pheromone binds to specific cell surface receptors on Saccharomyces cerevisiae a cells. The pheromone is then internalized, and cell surface receptors are down-regulated. At the same time, a signal is transmitted that causes changes in gene expression and cell cycle arrest. We show that the ability of cells to internalize alpha-factor is constant throughout the cell cycle, a cells are also able to respond to pheromone throughout the cycle even though there is cell cycle modulation of the expression of two pheromone-inducible genes, FUS1 and STE2. Both of these genes are expressed less efficiently near or just after the START point of the cell cycle in response to alpha-factor. For STE2, the basal level of expression is modulated in the same manner.

scholarly journals Studies on the role of specific cell surface receptors in the removal of lipoprotein (a) in man.

1983 ◽  
Vol 71 (5) ◽  
pp. 1431-1441 ◽  
Author(s):  
F Krempler ◽  
G M Kostner ◽  
A Roscher ◽  
F Haslauer ◽  
K Bolzano ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Surface Receptors ◽  
Specific Cell ◽  
Lipoprotein A ◽  
Surface Receptors ◽  
Specific Cell Surface

scholarly journals Negative Control of Cell Proliferation. Growth Arrest versus Apoptosis. Role of βGBP

1998 ◽  
Vol 1 (3) ◽  
pp. 169-173 ◽  
Author(s):  
Livio Mallucci ◽  
Valerie Wells
Keyword(s):  
Cell Surface ◽  
Growth Arrest ◽  
Inhibitory Effect ◽  
Negative Control ◽  
Cell Surface Receptors ◽  
Specific Cell ◽  
Surface Receptors ◽  
Growth Inhibitory ◽  
Cytostatic Factor ◽  
Apoptotic Pathways

βGBP is a novel physiological negative growth regulator of the cell and a cytostatic factor.It is secreted by cells, and bybinding with high affinity to specific cell surface receptors. In normal cell surface receptors. In normal cells, βGBP physiologically controls transition from G0to G1and passage from late S phase to G2by modulating signalling cascades activated by tyrosine Kinase receptors and by affecting transcription events.As a cytostatic Factor βGBP has a marked growth inhibitory effect on a variety of tumours including leukaemias where growth arrest is followed by the activation of apoptotic pathways and cell death.

scholarly journals Adeno-Associated Virus Capsids Displaying Immunoglobulin-Binding Domains Permit Antibody-Mediated Vector Retargeting to Specific Cell Surface Receptors

2002 ◽  
Vol 76 (9) ◽  
pp. 4559-4566 ◽  
Author(s):  
Martin U. Ried ◽  
Anne Girod ◽  
Kristin Leike ◽  
Hildegard Büning ◽  
Michael Hallek
Keyword(s):  
Cell Surface ◽  
Binding Domain ◽  
Cell Surface Receptors ◽  
Specific Cell ◽  
Broad Host Range ◽  
Adeno Associated Virus ◽  
Surface Receptors ◽  
Vector Targeting ◽  
Immunoglobulin Binding ◽  
Specific Cell Surface

ABSTRACT Recombinant adeno-associated virus type 2 (rAAV2) is a promising vector for human somatic gene therapy. However, its broad host range is a disadvantage for some applications, because it reduces the specificity of the gene transfer. To overcome this limitation, we sought to create a versatile rAAV vector targeting system which would allow us to redirect rAAV binding to specific cell surface receptors by simple coupling of different ligands to its capsid. For this purpose, an immunoglobulin G (IgG) binding domain of protein A, Z34C, was inserted into the AAV2 capsid at amino acid position 587. The resulting AAV2-Z34C mutants could be packaged and purified to high titers and bound to IgG molecules. rAAV2-Z34C vectors coupled to antibodies against CD29 (β1-integrin), CD117 (c-kit receptor), and CXCR4 specifically transduced distinct human hematopoietic cell lines. In marked contrast, no transduction was seen in the absence of antibodies or in the presence of specific blocking reagents. These results demonstrate for the first time that an immunoglobulin binding domain can be inserted into the AAV2 capsid and coupled to various antibodies, which mediate the retargeting of rAAV vectors to specific cell surface receptors.

scholarly journals Quantitation of alpha-factor internalization and response during the Saccharomyces cerevisiae cell cycle.

1991 ◽  
Vol 11 (10) ◽  
pp. 5251-5258 ◽  
Author(s):  
B Zanolari ◽  
H Riezman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Surface ◽  
Cell Surface Receptors ◽  
Specific Cell ◽  
Surface Receptors ◽  
Cycle Arrest ◽  
A Cells ◽  
Alpha Factor ◽  
Inducible Genes

The alpha-factor pheromone binds to specific cell surface receptors on Saccharomyces cerevisiae a cells. The pheromone is then internalized, and cell surface receptors are down-regulated. At the same time, a signal is transmitted that causes changes in gene expression and cell cycle arrest. We show that the ability of cells to internalize alpha-factor is constant throughout the cell cycle, a cells are also able to respond to pheromone throughout the cycle even though there is cell cycle modulation of the expression of two pheromone-inducible genes, FUS1 and STE2. Both of these genes are expressed less efficiently near or just after the START point of the cell cycle in response to alpha-factor. For STE2, the basal level of expression is modulated in the same manner.

Biological specificity and measurable physical properties of cell surface receptors and their possible role in signal transduction through the cytoskeleton

1995 ◽  
Vol 73 (7-8) ◽  
pp. 317-326 ◽  
Author(s):  
G. Forgacs
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Physical Properties ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Intracellular Signaling ◽  
Genetically Engineered ◽  
Cell Surface Receptors ◽  
Adhesive Properties ◽  
Surface Receptors

It is proposed that the binding specificities of cell adhesion molecules are manifested in their measurable physical properties. A method specifically designed to measure the interfacial tension of cell aggregates is described. With the introduction of a statistical mechanical model, the measured values of tensions for aggregates consisting of genetically engineered cells with controlled adhesive properties are used to obtain information on the strength of individual receptor–ligand bonds. The strength of binding must depend on the receptor and its ligand and reflects the amino acid sequence of the binding proteins. Many of the cell surface receptors, being transmembrane proteins, are attached to the various macromolecular networks of the cytoskeleton; therefore, it is suggested that their ligation and ensuing conformational change may substantially affect the mechanical state of the cytoskeletal assemblies. Since these assemblies are believed to actively participate in intracellular signaling by transmitting signals from the cell membrane into the nucleus, the cell adhesion molecules may influence signaling in a predictable way through their measurable physical characteristics. In particular, varying bond strength at the cell surface may lead to differential gene regulation.Key words: cell adhesion, surface tension, signaling, network, filament.

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