SYK and PDE4B control the effects of cAMP on AKT phosphorylation. (A) In the PDE4B-null DHL6 cell line, elevation of cAMP levels inhibit AKT phosphorylation (Ser473; left panel). Stable expression of a SYK gain-of-function mutant blocked cAMP-mediated inhibition of phospho-AKT. Anti-SYK immunoblot demonstrate the ectopic expression of this protein in the DHL6 cell line. These data suggest that constitutive activation of SYK may mimic the anti-inhibitory effects of PDE4B in DLBCL. (B,C) Western blot analyses of PDE4B overexpression in the DHL6 and knockdown in the OCI-Ly3 cell line, confirmed the central role of this phosphodiesterase in regulating cAMP-mediated AKT inhibition.