Protein Phosphatase 1, Regulatory Subunit 15B (PPP1R15B)

PPP1R15B promotes dephosphorylation of the transcription initiation factor EIF2-alpha (EIF2S1) through recruitment of protein phosphatase-1 (PP1) catalytic subunits. Ppp1r15b -/- mice showed low hematocrit and red blood cell count, with qualitative abnormalities in red cell size and shape. Histologic examination of mutant liver was consistent with compensatory proliferation of blood precursors. Ppp1r15b -/- mouse embryo fibroblasts showed elevated Eif2-alpha phosphorylation. Ppp1r15b -/- embryos that were also homozygous for an Eif2-alpha mutation that prevented Eif2-alpha phosphorylation were normalized, including elevated birth size and restored red blood cell count, compared with Ppp1r15b -/- embryos with wildtype Eif2-alpha.