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Updated: Aug 19, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Phorbol ester inhibition of hormonal induction of tyrosine aminotransferase
Abstract:
The liver specific enzyme, tyrosine aminotransferase, can be induced by glucocorticoids, cAMP analogs, or insulin. Each of these different inducing agents is believed to act through a separate pathway. The tumor promoting phorbol esters have been reported to stimulate phosphorylation of the insulin receptor and thereby decrease the ability of insulin to induce tyrosine aminotransferase. Our results demonstrate that TPA will not only inhibit the insulin stimulated increase in tyrosine aminotransferase, but will also inhibit induction of the enzyme by glucocorticoids or by cAMP.
Insights
Phorbol esters inhibit the liver enzyme tyrosine aminotransferase induction by insulin, glucocorticoids, and cAMP. This suggests a common pathway for these inducers, contrary to previous beliefs.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- Tyrosine aminotransferase is a liver-specific enzyme.
- Glucocorticoids, cAMP analogs, and insulin induce tyrosine aminotransferase via separate pathways.
- Phorbol esters are known to inhibit insulin's induction of this enzyme by affecting the insulin receptor.
Purpose of the Study:
- To investigate the effect of TPA (12-O-tetradecanoylphorbol-13-acetate) on tyrosine aminotransferase induction.
- To determine if TPA affects induction by agents other than insulin.
Main Methods:
- Enzyme assays to measure tyrosine aminotransferase activity.
- Treatment of liver cells with TPA, insulin, glucocorticoids, and cAMP analogs.
Main Results:
- TPA inhibited insulin-stimulated tyrosine aminotransferase induction.
- TPA also inhibited tyrosine aminotransferase induction by glucocorticoids.
- TPA inhibited tyrosine aminotransferase induction by cAMP analogs.
Conclusions:
- TPA inhibits tyrosine aminotransferase induction by multiple agents.
- These findings suggest a potential convergence or common regulatory mechanism for these induction pathways.
- This challenges the established model of separate pathways for insulin, glucocorticoid, and cAMP induction.
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