Bowman-Birk protease inhibitor reduces the radiation-induced activation of the EGF receptor and induces tyrosine phosphatase activity

Abstract

Purpose: To investigate the molecular action of the radioprotective Bowman-Birk protease inhibitor (BBI) on radiation-induced tyrosine kinase activity. Materials and methods: Radiation-induced activation of tyrosine kinases and phosphatases was measured in normal human skin fibroblasts by in vitro kinase assays after pre-incubation with BBI. Results: Pre-incubation with BBI resulted in a time-dependent block of the radiation-induced activation of tyrosine kinases. Whilst radiation-induced pp60c-Src activity was not modulated due to BBI pre-treatment, activation of epidermal growth factor receptor (EGFR) was inhibited. Additionally, pre-incubation with BBI resulted in enhanced tyrosine specific phosphatase (PTP) activity. Conclusions: BBI might exert its radioprotective activity by stabilizing specific tyrosine-phosphatases that interfere with EGFR activation in response to radiation exposure.