The pathway mediating insulin's effects on pyruvate dehydrogenase bypasses the insulin receptor tyrosine kinase
The effect of insulin on pyruvate dehydrogenase activity was examined in two different cell types that over expressed either normal or defective human insulin receptors, RAT 1 embryonic fibroblasts and Chinese hamster ovary (CHO) cells. Insulin stimulated pyruvate dehydrogenase activity in cells tha...
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Published in | The Journal of biological chemistry Vol. 266; no. 14; pp. 8814 - 8819 |
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Main Author | |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
15.05.1991
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Subjects | |
Online Access | Get full text |
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Summary: | The effect of insulin on pyruvate dehydrogenase activity was examined in two different cell types that over expressed either
normal or defective human insulin receptors, RAT 1 embryonic fibroblasts and Chinese hamster ovary (CHO) cells. Insulin stimulated
pyruvate dehydrogenase activity in cells that expressed normal insulin receptors (RAT 1 HIRc, and CHO-WT and CHO-T cells),
or receptors in which lysine 1018 in the ATP-binding site of the tyrosine kinase domain was exchanged for alanine (RAT 1 A/K1018
and CHO-mut cells). For both rat and hamster cell lines, the insulin dose-response curves from cells that expressed the mutant
receptors were identical to those from the appropriate controls that over expressed the normal insulin receptors. Insulin
failed to stimulate pyruvate dehydrogenase activity in CHO-delta cells, which expressed a mutant human insulin receptor that
was truncated by 112 amino acids at the carboxyl terminal of the beta chain. Control studies verified that all the cells used
in this study exhibited the expected phenotypes with respect to the number of insulin receptors which they expressed, insulin-stimulated
tyrosine kinase activity, and the biological consequences of inactivating the insulin receptor tyrosine kinase. These findings
show that the insulin receptor tyrosine kinase does not play an obligatory role in the insulin signaling pathway that stimulates
pyruvate dehydrogenase activity. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(18)31520-5 |