Here, while the extent of BCR dependent selleck chemicals Erlotinib Lyn activation by phos phorylation was treated as a measure of the strength of initial signal generated, the magnitude of Syk activation would then define the efficiency of its transduction to the downstream intermediates. The aim here was to identify the key parameter that might lead to weak activation of BCR dependent signals in immature B Here a is the forcing term representing the strength of the stimulation. At ground state a 0. In unstimulated cells, there is an equilibrium main tained between the active and inactive state of the sig naling molecules such as Lyn and Syk. However, Inhibitors,Modulators,Libraries it must be emphasized here that there are indeed multiple states of signaling intermediates present in the real system due to multiple phosphorylation sites.

But our focus here was to analyze the balance between the active and inactive forms of the species and their differ ential response to varying basal activity. Therefore in the considered scenario, Inhibitors,Modulators,Libraries mathematically, at ground state i. e, a 0, we define the basal value of active Lyn denoted by Lp as the value where, cells, as opposed Inhibitors,Modulators,Libraries to that in mature B cells. More specifi cally, we wanted to determine whether the higher levels of basally active Lyn in immature B cells could account for this difference. In our model, we also incorporated the role of SHP 1 as a negative regulator of BCR signal ing. It is now widely accepted that receptor associated phosphatases function as key negative regulators that keep the system Inhibitors,Modulators,Libraries in steady state in the absence of an activating ligand.

Following engagement of the receptor, however, there is a transient decrease in the negative regulatory activity of this phosphatase, after which it again returns to its initial value. Thus, if Lp denotes the concentration of activated Lyn molecule. Sm that of the Syk molecule susceptible to activation Inhibitors,Modulators,Libraries by phosphor ylation. and Sp denotes the concentration of activated Syk, the model with the meaning of each parameter can be written as follows Using the definition of Lp if we solve the equation we get the value of Lp as given below, Thus our mathematical result suggests that, at ground state, the basal value is inversely related to the magni tude of the negative regulator acting on the activated Lyn molecule. We next simulated our model system and the results for Lyn and Syk activation are shown in Figure 7A and 7B.

Here, we calculated the value of Lp from the derived relation. We found that the influence of the negative regulator on Lyn and Syk activity produced two different basal states for them before the trigger point, which Kyprolis denotes BCR dependent stimulation. But the interesting prediction from the model was that the sensitivity of either Lyn or Syk response to BCR engagement was sig With initial conditions Lp 0, Sm 0, Sp 0.