High levels of cytosolic free calcium inhibit dephosphorylation of insulin receptor and glycogen synthase.
Treatment of adipocytes with depolarizing concentrations of K+ (40 mM) for 60 min increased [Ca2+]i from 158 +/- 28 nM to 328 +/- 38 nM. This significantly reduced (up to 80% inhibition) dephosphorylation of insulin receptor (IR), EGF receptor (EGF-R) and glycogen synthase (GS). The calcium channel blocker, nitrendipine (30 microM), or Ca2+ free medium completely prevented K(+)-induced inhibition of phosphoprotein phosphatase (PPTase). This effect of high [Ca2+]i was completely reversible when the cells were returned into the non-depolarizing medium. Trypsin treatment (4 micrograms/ml) of the membrane fraction containing inhibited PPTase activity, restored dephosphorylation activity to normal suggesting that elevated [Ca2+]i may inhibit PPTase by promoting its association with the inhibitors. These observations indicate that dephosphorylation of IR and GS can be regulated by [Ca2+]i.
Begum
N
N
Department of Medicine, University of Colorado Health Sciences Center, Denver.
Sussman
K E
KE
Draznin
B
B
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D066246:ErbB Receptors / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D016257:Fura-2; D006006:Glycogen Synthase / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000737:chemistry; D008297:Male; D008564:Membrane Potentials; D009568:Nitrendipine / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D011188:Potassium / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology; D014909:Wheat Germ Agglutinins
D014909:Wheat Germ Agglutinins; D009568:Nitrendipine; D006006:Glycogen Synthase; D066246:ErbB Receptors; D011972:Receptor, Insulin; D010749:Phosphoprotein Phosphatases; D014357:Trypsin; D011188:Potassium; D002118:Calcium; D016257:Fura-2