We next evaluated the impact of dasatinib on basal and BCR induced level of EGR 1 as a target of JNK. All measurements were completed in duplicate and the mean value is provided. Jointly, these indicate that EGR 1 is really a downstream goal MAPK activation of JNK in MCL cells and that JNK promoted constitutive and BCR induced cell survival in MCL implicating particularly EGR 1 induction. Inhibition of LYN activity is associated with a rise of apoptosis in MCL cells The BCR signal is initially transmitted by LYN kinase resulting in activation of numerous signaling pathways including JNK. We consequently considered the activation status of LYN in MCL cells and its involvement in cell survival. Using an anti phospho SFK realizing the catalytic site of several Src kinases among which the Tyr397 of LYN, we found in 9 out of 10 UPN cases tried such a specific signal to variable extents of constitutive phosphorylation forming a 53 56 kDa doublet. We established that doublet corresponded to phospho LYN by an immunoprecipitation assay using an anti LYN antibody. Considering the constitutive activation of LYN in MCL Neuroblastoma cells, we next evaluated the effect of PP2, an artificial pyrazolopyrimidine selective inhibitor of SFK, and dasatinib, a dental multiple kinase inhibitor which also prevents the transautophosphorylation of the energetic Tyr397 residue of LYN. Therapy of primary cells with PP2 or dasatinib led to a dose dependent decrease of Tyr397 LYN phosphorylation and complete inhibition was achieved up to 10 uM and 100nM for PP2 and dasatinib respectively. Inhibition of phospho Tyr397 LYN by PP2 was associated with a significant and dose-dependent increase of apoptosis rate cells respectively, p 0. 006, n 6. Treatment with dasatinib for 24 h also led to a significant and dose-dependent increase of apoptosis deubiquitinating enzyme inhibitor cells, respectively, p 0. . 0001, d 7. Incredibly, dasatinib had little apoptosis effect on phospho Tyr397 LYN negative cells in a concentration as much as 200nM. Altogether, these show that MCL cells exhibit a constitutive phosphorylation of BCR associated LYN and that treatment with dasatinib or PP2 suppressed LYN service and increased spontaneous apoptosis. Inhibition of the BCR induced LYN phosphorylation by PP2 or dasatinib is associated with an elimination of BCRmediated cell survival Since PP2 and dasatinib effortlessly blocked activation of BCR associated LYN in MCL cells, we next considered the effect of the compounds on JNK phosphorylation, EGR 1 expression and on cell survival upon BCR engagement. A powerful increase of phospho Tyr397 LYN was seen in a reaction to BCR ligation and therapy with dasatinib while SP600125 that affect JNK didn’t completely blocked this effect, as shown in Figure 5A. Equally, PP2 decreased BCR induced phospho Tyr397 LYN in primary MCL cells. Dasatinib also paid down as a downstream target of LYN BCR caused phospho JNK p46, positioning JNK in response to BCR engagement.