We next examined the effect of dasatinib on basal and BCR induced level of EGR 1 as a target of JNK. All measurements were performed in duplicate and the mean value is provided. Collectively, these suggest that EGR 1 is a downstream target E2 conjugating of JNK in MCL cells and that JNK endorsed constitutive and BCR induced cell survival in MCL implicating significantly 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 ultimately causing activation of numerous signaling pathways including JNK. We therefore examined the initial status of LYN in MCL cells and its involvement in cell survival. Utilizing an anti phospho SFK realizing the catalytic site of several Src kinases among that the Tyr397 of LYN, we found in 9 out of 10 UPN circumstances examined such a certain sign to variable extents of constitutive phosphorylation forming a 53 56 kDa doublet. We proved this doublet corresponded to phospho LYN by an immunoprecipitation assay utilizing an anti LYN antibody. Considering the constitutive activation of LYN in MCL PTM cells, we next evaluated the influence of PP2, a synthetic pyrazolopyrimidine selective inhibitor of SFK, and dasatinib, a dental multiple kinase inhibitor which also prevents the transautophosphorylation of the active Tyr397 residue of LYN. Therapy of primary cells with PP2 or dasatinib resulted in a dose-dependent loss of Tyr397 LYN phosphorylation and total inhibition was reached as much as 10 uM and 100nM for dasatinib and PP2 respectively. Inhibition of phospho Tyr397 LYN by PP2 was of a significant and dose-dependent increase of apoptosis price cells respectively, g 0. 006, n 6. Therapy with dasatinib for 24 h also generated a substantial and dose-dependent increase of apoptosis Checkpoint inhibitor cells, respectively, p 0. . 0001, n 7. Incredibly, dasatinib had small apoptosis impact on phospho Tyr397 LYN negative cells in a concentration as much as 200nM. Completely, these indicate that MCL cells show a phosphorylation of BCR related LYN and that treatment with dasatinib or PP2 suppressed LYN activation and increased spontaneous apoptosis. Inhibition of the BCR induced LYN phosphorylation by PP2 or dasatinib is associated with a withdrawal of BCRmediated cell survival Since PP2 and dasatinib effectively blocked activation of BCR associated LYN in MCL cells, we next considered the effect of these compounds on JNK phosphorylation, EGR 1 expression and on cell survival upon BCR engagement. As shown in Figure 5A, a solid increase of phospho Tyr397 LYN was seen in reaction to BCR ligation and therapy with dasatinib while SP600125 that influence JNK didn’t completely blocked this effect. Similarly, PP2 lowered BCR induced phospho Tyr397 LYN in major MCL cells. Dasatinib also lowered BCR caused phospho JNK p46, placing JNK as a downstream target of LYN in a reaction to BCR engagement.