Phosphorylation of glycolytic and gluconeogenic enzymes by the insulin receptor kinase

✍ Scribed by Elizabeth M. Sale; Morris F. White; C. Ronald Kahn

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: English
• Weight: 708 KB
• Volume: 33
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240330103

✦ Synopsis

Various glycolytic and gluconeogenic enzymes were tested as substrates for the insulin receptor kinase. Phosphofructokinase and phosphoglycerate mutase were found to be the best substrates. Phosphorylation of these enzymes was rapid, stimulated 2-to 6-fold by M insulin and occurred exclusively on tyrosine residues. Enolase, fructose 1,6-bisphosphatase, lactate dehydrogenases in decreasing order, were also subject to insulin-stimulated phosphorylation but to a smaller extent than that for phosphofructokinase or phosphoglycerate mutase.

The phosphorylation of phosphofructokinase was studied most extensively since phosphofructokinase is known to catalyze a rate-limiting step in glycolosis. The apparent Km of the insulin receptor for phosphofructokinase was 0.1 pM, which is within the physiologic range of concentration of this enzyme in most cells. Tyrosine phosphorylation of phosphofructokinase paralleled autophosphorylation of the &subunit of the insulin receptor with respect to time course, insulin dose response (half maximal effect between lop9 and lo-' M insulin), and cation requirement (Mn2+ > Mg2+ > > Ca2+). Further study will be required to determine whether the tyrosine phosphorylation of phosphofructokinase plays a role in insulin-stimulated increases in glycolytic flux.