RESUMEN
CEACAM1 is a signal-regulating, homophilic cell adhesion receptor system expressed in epithelia, vessel endothelia, and leukocytes. Here, we demonstrate that CEACAM1 is expressed also in PC12 cells, both as the common transmembrane isoforms, CEACAM1-L and CEACAM1-S, and as a novel, secreted, differentially spliced isoform. CEACAM1 can have both positive and negative effects on cell signaling. In an attempt to explain this dual behavior, we have initiated computational analysis of the signal-regulating effects of CEACAM1. This suggests that CEACAM1 can exert its signal-regulating activities by discriminating between binding of Src kinases and SHP phosphatases, respectively. Major factors that regulate this discrimination are the expression levels and expression ratios of transmembrane CEACAM1-L and CEACAM1-S, the concentration of secreted CEACAM1, and homophilic binding of CEACAM1 presented by neighboring cells.
Asunto(s)
Antígenos CD/fisiología , Antígenos de Diferenciación/fisiología , Biología Computacional/métodos , Transducción de Señal , Secuencias de Aminoácidos , Animales , Adhesión Celular , Moléculas de Adhesión Celular , Relación Dosis-Respuesta a Droga , Péptidos y Proteínas de Señalización Intracelular , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Modelos Químicos , Células PC12 , Fosforilación , Unión Proteica , Isoformas de Proteínas , Estructura Terciaria de Proteína , Proteína Tirosina Fosfatasa no Receptora Tipo 6 , Proteínas Tirosina Fosfatasas/metabolismo , Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , RatasRESUMEN
We developed a model of 545 components (nodes) and 1259 interactions representing signaling pathways and cellular machines in the hippocampal CA1 neuron. Using graph theory methods, we analyzed ligand-induced signal flow through the system. Specification of input and output nodes allowed us to identify functional modules. Networking resulted in the emergence of regulatory motifs, such as positive and negative feedback and feedforward loops, that process information. Key regulators of plasticity were highly connected nodes required for the formation of regulatory motifs, indicating the potential importance of such motifs in determining cellular choices between homeostasis and plasticity.