| Author Summary | We analyzed a large number phosphorylated proteins in neuroblastoma cells to discern patterns that indicate functional signal transduction pathways. |
| Compartmentalization and Collaboration in RTK Signaling Pathways | Our data suggest that SFKs, especially FYN and LYN, function as signal integrating devices—central hubs in the tyrosine kinase signaling network—to distinguish RTK signal transduction pathways, in part by activating distinct mechanisms specifically in endosomes and lipid rafts. |
| Compartmentalization and Collaboration in RTK Signaling Pathways | Phosphorylation on selected sites would be consistent with RTKs acting as effectors as well as initiators of signal transduction ; other tyrosine kinases, such as other RTKs or SFKs, may favor phosphorylation on particular sites. |
| E Iy_s E_1 E E DRM cyt c nggTN c SCF PTN F NF F NF F NF F NF P1M FYN '-WB: *“’ ' 0 ~ - -° LYN?” FYN PTN G 8 O . O o . ' _ ‘—§ 8 2 O _ _ c ° to o - g o LYN .E V '5 o - . - - -PTN g N 3 o H FYN PTN FYN SCF LYN PTN LYN SCF <0 a) l!) U) : <1-(5 .C on U 2 ~ ii Iii lili i ills i q I | Phosphorylation on selected sites would be consistent With RTKs acting as effectors as well as initiators of signal transduction . |
| Introduction | Interactions between proteins that contain SH2 and SH3 domains indicate that tyrosine kinase signaling and endocytosis are linked, and there is good evidence that endocytosis and signal transduction in general are integrated [30,31]. |
| Neuroblastoma Phosphoproteomic Network | Nevertheless, PPI network analysis indicates that the phosphoproteomic data are complete enough to examine further to gain insight into signal transduction pathways that are active in neuroblastoma (S2 Fig). |
| Discussion | Recent experimental observations suggest that also paracrine IL-2 signals towards other Th cells are important for regulation of immune responses, while true au-tocrine IL-2 signals are suppressed by the intracellular signal transduction pathway [5,37]. |
| Discussion | Fold-changes in sensory biological systems are a classical phenomenon referred to as Weber’s law, and were recently observed in various intracellular signal transduction pathways [60—63]. |
| Introduction | Although IL-2 secreting Th cells upregulate CD25, Long and Adler [37] reported that they lack phosphorylated STAT5, a key intermediate in the IL-2R signal transduction cascade. |
| Introduction | In the same experiment, other Th cells not secreting IL-2 also upregulate CD25 in response to IL-2, and in addition show fully functional signal transduction [5,37]. |
| ln-silico Th cell culture exhibits localized paracrine lL-2 signaling | Under these conditions it would take hours to induce a reliable signal, indicating that bulk cytokine concentrations might just be capable of, or even be too low for, stimulating signal transduction . |
| Discussion | Phagocytosis is particularly complex as it is affected by quantitative changes in host signal transduction molecules [31], cytoskeletal dynamics [32], particle receptor affinity [6] , host receptor density, particle size, and shape [33]. |
| Introduction | In contrast, the creation and resolution of the phagocytic cup is a dynamic process involving numerous signal transduction and structural genes coordinated in receptor clustering, membrane phospho-lipid redistribution, and cytoskeletal reorganization [4] (81 Table). |
| Introduction | cell surface, signal transduction network, cytoskeleton) that have stochastic [14] and deterministic [15] origins. |