Platelet-derived growth factor (PDGF) rapidly stimulates binding of glycolytic enzymes to muscle cytoskeleton, prevented by calmodulin antagonists.
Glycolytic enzymes are known to be controlled by reversible binding to cytoskeleton. Our previous experiments have shown that insulin, epidermal growth factor (EGF), and Ca2+ induce a rapid and transient stimulation of binding of glycolytic enzymes to muscle cytoskeleton. We show here that platelet-derived growth factor (PDGF) exerts a similar action. Incubation of rat diaphragm muscle in the presence of PDGF resulted in rapid and transient stimulation of binding of phosphofructokinase (EC 2.7.11) and aldolase (EC 4.1.2.13) to muscle cytoskeleton. The increase in cytoskeleton-bound glycolytic enzymes induced by PDGF was prevented by treatment with the calmodulin antagonists trifluoperazine or CGS 9343B (a potent and selective inhibitor of calmodulin activity), which strongly suggests that Ca(2+)-calmodulin is involved in this effect of PDGF. Similarly, we previously found that stimulation of cytoskeleton-bound glycolytic enzymes exerted by insulin, EGF, or Ca2+, was also calmodulin mediated. The present and previous results suggest that the rapid, Ca(2+)-calmodulin-mediated increase in cytoskeleton-bound glycolytic enzymes, may be a general mechanism in the cell, in signal transduction of insulin, growth factors, and other Ca(2+)-mobilizing hormones. The accelerated cytoskeletal glycolysis will provide local ATP, which is required for the rapid cytoskeletal-membrane rearrangements following binding of growth factor or hormone to its receptor.
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; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003599:Cytoskeleton / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D009130:Muscle, Smooth / Q000378:metabolism* / Q000648:ultrastructure; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D013268:Stimulation, Chemical; D013997:Time Factors
D002147:Calmodulin; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D004815:Epidermal Growth Factor; D010732:Phosphofructokinase-1; D005634:Fructose-Bisphosphate Aldolase; D002118:Calcium