the disruption of rafts completely inhibits the signal transduction .

Thereby an increase of the intracellular ROS level releases the redox-sensitive binding between NRX and DVL, hence promoting a DVL-mediated stimulation of the downstream WNT/fi-catenin signal transduction , which eventually leads to the well known fi-catenin accumulation in the nucleus.

Whereas extensive ROS stimulation may cause oxidative stress and cell damage, it is meanwhile well accepted, that ROS can also act as intracellular messenger inducing redox-sensitive signal transductions when present at physiological concentrations [54].

DVL as a concentration-dependent dual signal transducer .

The WNT/fi-catenin signal transduction is characterized by a reaction cascade, that is initiated by extracellular WNT molecules and eventually leads to an accumulation of cy-tosolic fi-catenin and its subsequent shuttling into the nucleus.

One of the key mechanisms of the WNT signal transduction is the formation of a large pro-tein-receptor complex, called signalosome, in response to the extracellular WNT stimulus [9, the signalosome triggers the phosphorylation of several intracellular phosphorylation sites (mainly PPSPXS motifs) in the cytosolic tail of LRP6, generating high-density platforms for the recruitment of AXIN [11—13].

As demonstrated by earlier and recent studies, the deployment of lipid rafts from the plasma membrane prevents the raft dependent LRP6 phosphorylation and thereby inhibits the WNT induced receptor activation and subsequent signal transduction [15, 17] , which could eXplain the inhibition of WNT/fi-catenin signaling by MbCD treatment after 3 hours.

During our investigations we found that lipid raft disruption by Methyl-fi-Cyclodextrin (MbCD) effectively inhibits WNT/fi-catenin signal transduction .

We analyzed a large number phosphorylated proteins in neuroblastoma cells to discern patterns that indicate functional signal transduction 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.

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.

Phosphorylation on selected sites would be consistent With RTKs acting as effectors as well as initiators of signal transduction .

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].

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).

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].

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].

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.

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].

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 .

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].

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).

cell surface, signal transduction network, cytoskeleton) that have stochastic [14] and deterministic [15] origins.