These collective results, therefore, confirm that activity of the BCR associated SHP 1 was indeed under negative control of the co associated p38. This, in turn, provides a likely explanation selleck screening library for the increased levels of activated Lyn detected in un stimulated CH1 cells. Extracting the core cellular network that mediates BCR dependent cell cycle arrest CH1 cells Our results so far had helped Inhibitors,Modulators,Libraries to characterize at least some of the intermediates that were involved during anti IgM induced signal transduction. In subsequent experiments, we were also able to define the key set of TFs that were responsible for translating the pattern of signaling events generated into the expression of those target genes that were, at least primarily, involved in driving the G1 phase arrest.

Having thus generated the molecular map of the network emanating from the BCR and extending up to the enforcement of the specific cel lular response, we then also identified a feedback inter action Inhibitors,Modulators,Libraries between p38 and SHP 1 that functioned, through the regulation of Lyn activity, as a key regulatory motif of this network. These cumulative results, therefore, allowed us to further refine the rather generic network map derived in Figure 3C, and obtain a more precise description of the BCR dependent regulatory network for G1 arrest in CH1 cells. By combining known experimental pathway information on B cell signaling, and the network derived through Inhibitors,Modulators,Libraries a shortest path analysis, we could generate the CH1 cell specific signaling axis responsible for driving G1 arrest.

Further, we could also distinguish the individual stages based on the sequential steps of initiation, propagation, and integration of intracellular signal transduction cascades. The step of signal initiation is considered Inhibitors,Modulators,Libraries to represent the early events that occur upon receptor engagement, and this early upstream process regulates the downstream targets both qualitatively and quantitatively. A mathematical model helps to define key regulators of system homeostasis and Lyn activation Although we could successfully prove the role of p38 in regulation of Lyn by acting on SHP 1, it did not address the issue of cell type specificity in determining cell fate decisions. It has been reported that levels of phospho Lyn and other intermediates are significantly higher in immature B cell compared to the mature coun To take into account the particular nature of the negative regulator as discussed above we assumed, terpart cells.

We also observed this feature in our present study, when compared with our earlier studies involving Inhibitors,Modulators,Libraries mature B cells. Since we had sufficient information on both mature and immature counterparts regarding their basal status and the way they respond to the selleck catalog antigen we sought to build a mathematical model representing the fundamental differences in both of these cell types, in terms of the initiation of BCR signaling.