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Tyrphostins inhibit the epidermal growth factor receptor‐mediated breakdown of phosphoinositides
Author(s) -
Posner Israel,
Gazit Aviv,
Gilon Chaim,
Levitzki Alexander
Publication year - 1989
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(89)81554-6
Subject(s) - epidermal growth factor , a431 cells , epidermoid carcinoma , biology , endocrinology , medicine , receptor , microbiology and biotechnology , biochemistry , chemistry , cell , cell cycle , cancer , molecular medicine
In response to epidermal growth factor (EGF) and the Ca 2+ ionophore A23187, the total phosphatidylinositides (IPT) increased in A431 human epidermoid carcinoma cells 1.8‐ and 2.0‐fold and in the EGF‐dependent A431/Clone 15‐2 cells 3.0‐ and 8.0‐fold, respectively, over basal levels. Both responses were inhibited by the antiproliferative agents tyrphostins, but the EGF‐induced increase in IP T was inhibited to a much greater extent than that induced by the ionophore. Tyrphostins which are potent EGF‐receptor kinase inhibitors were also potent in blocking the EGF‐induced production of phosphoinositides. The less potent tyrphostins were found to inhibit the EGF‐dependent IP T formation more weakly. These results support the notion that phospholipase C is activated through its phosphorylation by the EGF receptor. Tyrphostins; Epidermal growth factor; Phospholipase C phosphorylation; Ca 2+ ionophore; (A431 cell, A431/Clone 15‐2 cell)