PDE4B-dependent cAMP inhibition of SYK in DLBCL. (A) Western blot analyses show a marked inhibition of phospho-SYK (Tyr525/526) levels after elevation of intracellular levels of cAMP with the adenylyl cyclase activator Forskolin. These effects are present in PDE4B-low but not in PDE4B-high DLBCL cell lines. Total SYK expression confirms equal loading. (B) Exposure of DLBCL cell lines to the cell-permeable synthetic 8-Br-cAMP also significantly decreased SYK phosphorylation confirming the specificity of Forskolin effects. (C) FACS analysis shows that cAMP inhibits intracellular expression of phospho-BLNK (Tyr84), a direct SYK target, in a PDE4B-dependent manner. A 43%, 34%, and 37% decrease in the mean phospho-BLNK expression was detected in DHL6, DHL10, and WSU-NHL, respectively.