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Stimulation of p85/RING3 kinase in multiple organs after systemic administration of mitogens into mice
J Ostrowski1, S K Florio, G V Denis
1Department of Medicine, University of Washington, Seattle 98195, USA.
Abstract:
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.
Insights
A novel 85 kDa kinase (p85) activated by growth factors in multiple organs may play a role in proliferative diseases like leukemia. This kinase is likely identical to the RING3 kinase found in leukocytes.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Signaling
Background:
- Kinase activation is crucial for cellular processes.
- Aberrant kinase activity is implicated in various proliferative diseases, including leukemia.
- The RING3 kinase is known for its high activity in leukocytes.
Purpose of the Study:
- To investigate kinase activation in different organs following mitogen and cytokine administration.
- To identify and characterize novel kinases involved in cellular signaling pathways.
- To explore the potential role of identified kinases in disease pathogenesis.
Main Methods:
- Autophosphorylation membrane assay to detect kinase activity.
- Intraperitoneal injections of mitogens (EGF, PMA) and cytokines (IL-1beta) in mice.
- Immunoprecipitation using antibodies against RING3 kinase.
Main Results:
- Epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA), and interleukin-1beta (IL-1beta) activated multiple kinases across various organs.
- A prominent 85 kDa kinase (p85) was activated by all tested agents in the lung, kidney, brain, liver, and heart.
- p85 kinase exhibited indistinguishable properties from RING3 kinase, and immunoprecipitation confirmed their identity.
- p85/RING3 kinase activation by growth factors suggests its involvement in proliferative diseases.
Conclusions:
- The p85/RING3 kinase is activated by growth factors and cytokines in multiple organs.
- p85/RING3 kinase is a potential therapeutic target for leukemias and other proliferative disorders.
- Further research is warranted to elucidate the precise role of p85/RING3 kinase in disease.