Stimulatory effect of epidermal growth factor on binding of glycolytic enzymes to muscles cytoskeleton and the antagonistic action of calmodulin inhibitors.
We report here on a novel mechanism involved in epidermal growth factor (EGF) action, which shows that EGF rapidly stimulates binding of the glycolytic enzymes, phosphofructokinase (EC 2.7.1.11), and aldolase (EC 4.1.2.13) to muscle cytoskeleton. This effect was demonstrated both in vivo, in the tibialis anterior muscle from rats injected with EGF, and in vitro, in the isolated rat diaphragm muscle incubated with EGF. The increase in cytoskeleton-bound glycolytic enzymes induced by EGF was prevented, in both the in vivo and in vitro experiments, by treatment with the calmodulin antagonists trifluoperazine or CGS 9343B (a potent and selective inhibitor of calmodulin activity), which strongly suggests that Ca2+ and calmodulin are involved in this effect of EGF. Our previous findings have revealed that insulin or Ca2+ exert a similar rapid stimulation of cytoskeletal glycolysis, which is also calmodulin mediated. We now hypothesize that this may be a general mechanism of signal transduction in the cell, involving Ca(2+)-mobilizing hormones and growth factors, and supplying local ATP, in the vicinity of cytoskeleton-membrane, which is required for the rapid cytoskeletal-membrane rearrangements upon membrane-induced events.
Department of Life Sciences Bar-Ilan University, Ramat Gan, Israel.
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Livnat
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Chen-Zion
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Beitner
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D066298:In Vitro Techniques; D009132:Muscles / Q000187:drug effects / Q000201:enzymology*; D010732:Phosphofructokinase-1 / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D012132:Respiratory Muscles / Q000187:drug effects / Q000201:enzymology; D014268:Trifluoperazine / Q000494:pharmacology
D001562:Benzimidazoles; D002147:Calmodulin; C052087:CGS 9343B; D014268:Trifluoperazine; D004815:Epidermal Growth Factor; D010732:Phosphofructokinase-1; D005634:Fructose-Bisphosphate Aldolase; D002118:Calcium