Stimulation of p85/RING3 kinase in multiple organs after systemic administration of mitogens into mice.

Using an autophosphorylation membrane assay, we examined activation of kinases in different organs after intraperitoneal injections of mitogens and cytokines into mice. In the multiple organs examined administration of either epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA) or interleukin-1beta (IL-1beta) activated a number of kinases. Most notably among those was a kinase of approximately 85 kDa (p85) that was activated by EGF, PMA and IL-1beta in the lung, kidney, brain, liver and heart. The size and properties of this enzyme are indistinguishable from the RING3 kinase that has a very high activity in leukocytes of patients with leukemia. In animals treated with PMA, antibodies against RING3 kinase immunoprecipitated PMA-responsive p85 activity from the lung and brain suggesting that p85 and RING3 kinases are the same enzymes. Activation of p85/RING3 kinase by growth factors in multiple organs might reflect involvement of this enzyme in the pathogenesis of leukemias and other proliferative diseases.