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1.
Ann N Y Acad Sci ; 908: 133-42, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10911954

ABSTRACT

Aging is a universal and inevitable phenomenon that affects nearly all animal species. It can be considered the product of an interaction between genetic, environmental, and lifestyle factors, which in turn influence longevity that varies between and within species. It has been proposed not only that the aging process is under genetic control, but that it can also be considered a result of the failure of homeostasis due to the accumulation of damage. This review article discusses these issues, focusing on the function of genes that associate with aging and longevity, as well as on the molecular mechanisms that control cell survival and maintenance during aging.


Subject(s)
Aging/genetics , Aging/physiology , Animals , Cell Death , Cell Survival , Homeostasis/physiology , Humans , Longevity/genetics , Longevity/physiology , Proteins/metabolism , Signal Transduction/physiology
2.
Mol Cell Neurosci ; 13(6): 441-9, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10383829

ABSTRACT

Receptor-like protein tyrosine phosphatase kappa (RPTPkappa) is expressed in the nervous system in a manner consistent with a role in axonal growth and guidance. The extracellular domain of RPTPkappa shares structural features with cell adhesion molecules and can support homophilic adhesion. In the present study we produced a soluble Fc-chimeric protein containing the full extracellular domain of RPTPkappa. Following affinity capture, the RPTPkappa-Fc was shown to promote the aggregation of Covasphere beads, confirming its homophilic binding activity. When added to cultures of cerebellar neurons as a soluble molecule, the RPTPkappa chimera stimulated neurite outgrowth. The neurite outgrowth response was substantially inhibited by a cell-permeable peptide inhibitor of Grb2 and by PD 098059, a drug that has been used to inhibit MEK1 activation in a wide range of cell types. These results demonstrate that RPTPkappa can stimulate neurite outgrowth and provide evidence that this might involve the coupling of Grb2 to a MAPK signal transduction cascade.


Subject(s)
Adaptor Proteins, Signal Transducing , Mitogen-Activated Protein Kinase Kinases , Neurites/drug effects , Protein Serine-Threonine Kinases/metabolism , Protein Tyrosine Phosphatases/pharmacology , Protein-Tyrosine Kinases/metabolism , Proteins/metabolism , 3T3 Cells , Animals , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cells, Cultured , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , GRB2 Adaptor Protein , Immunoglobulin Fc Fragments/genetics , MAP Kinase Kinase 1 , Mice , Molecular Sequence Data , Neurons/cytology , Neurons/drug effects , Peptides/pharmacology , Protein Tyrosine Phosphatases/genetics , Proteins/antagonists & inhibitors , Rats , Receptor-Like Protein Tyrosine Phosphatases, Class 2 , Receptors, Fibroblast Growth Factor/metabolism , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/pharmacology , Signal Transduction/drug effects
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