RESUMO
The ataxia telangiectasia mutated (ATM) gene encodes a serine/threonine protein kinase that plays a critical role in genomic surveillance and development. Here, we use a peptide library approach to define the in vitro substrate specificity of ATM kinase activity. The peptide library analysis identified an optimal sequence with a central core motif of LSQE that is preferentially phosphorylated by ATM. The contributions of the amino acids surrounding serine in the LSQE motif were assessed by utilizing specific peptide libraries or individual peptide substrates. All amino acids comprising the LSQE sequence were critical for maximum peptide substrate suitability for ATM. The DNA-dependent protein kinase (DNA-PK), a Ser/Thr kinase related to ATM and important in DNA repair, was compared with ATM in terms of peptide substrate selectivity. DNA-PK was found to be unique in its preference of neighboring amino acids to the phosphorylated serine. Peptide library analyses defined a preferred amino acid motif for ATM that permits clear distinctions between ATM and DNA-PK kinase activity. Data base searches using the library-derived ATM sequence identified previously characterized substrates of ATM, as well as novel candidate substrate targets that may function downstream in ATM-directed signaling pathways.
Assuntos
Biblioteca de Peptídeos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Dados de Sequência Molecular , Fosfatidilinositol 3-Quinases/química , Fosforilação , Proteínas Serina-Treonina Quinases/química , Especificidade por Substrato , Células Tumorais Cultivadas , Proteínas Supressoras de TumorAssuntos
Linfoma/genética , Proteínas Serina-Treonina Quinases , Proteínas/genética , Ataxia Telangiectasia/complicações , Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular , Transformação Celular Neoplásica , Proteínas de Ligação a DNA , Humanos , Linfoma/etiologia , Mutação , Biblioteca de Peptídeos , Proteínas/metabolismo , Transdução de Sinais , Proteínas Supressoras de TumorRESUMO
This is the second progress report on the webometry project: acquisition of data regarding the density of links on the world-wide web (WWW). We illustrate the primary visualization strategy, the synergy matrix, in the case of a model subnet of nine nodes.
Assuntos
Redes de Comunicação de Computadores/organização & administração , Redes de Comunicação de Computadores/tendências , Redes Neurais de ComputaçãoRESUMO
To create a complex dynamical model for a complex system, it is normally necessary to have a directed graph of the network, a dynamical model for each node, and a coupling function for each directed edge. But in many applications, the only observable data consists of communications from one node to another. In this situation, the modeler may infer a complex dynamical model for the network without any explicit knowledge of the independent dynamical behavior of the component systems (nodes). Here we present one procedure for this type of modeling problem, inspired by the attractor reconstruction procedure of chaos theory. Part of this proposal consists of a strategy for computer graphic presentation of the interactive dynamics of the complex system (or social network of dynamical schemes) called a netscope. We can imagine applications to diverse situations, such as decision groups, management, forecasting, international relations, classroom monitoring, therapy (personal, family, group, etc.) and distributed processors, to name a few.
Assuntos
Comunicação , Modelos Psicológicos , Psicoterapia , Simulação por Computador , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Gravação em Fita , Comportamento VerbalRESUMO
A framework is presented here for constructing dynamical systems models of physiological processes. Concepts such as serial coupling and dynamical control are defined, and several applications are sketched.
