Figure 5.
PRAK deficiency leads to hyper-activation of JNK and increased cell proliferation in vivo. Immunohistochemical analysis of phospho-JNK-T183/Y185 (A, B-top panel, and C) and Ki-67 (B-bottom panel) in spleens of terminally ill Eμ-N-RasG12D;PRAK+/+, Eμ-N-RasG12D;PRAK+/−, and Eμ-N-RasG12D;PRAK−/− littermates (A), 6-month-old PRAK+/+, Eμ-N-RasG12D;PRAK+/+, PRAK−/−, and Eμ-N-RasG12D;PRAK−/− littermates (B), or 9-week-old Eμ-N-RasG12D;PRAK+/+ and Eμ-N-RasG12D;PRAK−/− littermates (C). Arrows indicate examples of cells positive for phospho-JNK (A-top panels and C-left panels), Bar graphs represent positive cells quantified under microscope in 20 randomly chosen 40X-fields. Numbers are mean ± SD. Statistical significance was determined by unpaired t test. Western blot analysis was performed to measure the phospho-JNK and JNK levels in spleens of 9-week-old Eμ-N-RasG12D;PRAK+/+ and Eμ-N-RasG12D;PRAK−/− littermates (C-bottom right panels).