The protein tyrosine phosphatase LAR has a major impact on insulin receptor dephosphorylation.
Transmembrane protein tyrosine phosphatases (PTPases) may act as regulators of the insulin receptor. Supporting this hypothesis, antisense suppression of the PTPase LAR in McA-RH7777 hepatoma cells increased insulin receptor signaling (Kulas et. al., J. Biol. Chem. (1996) 271, 748-754). The effects of decreased LAR expression may be mediated by decreased dephosphorylation of the insulin receptor. The rate of insulin receptor dephosphorylation was examined in situ, following elution of surface bound insulin at pH 4.0. In LAR antisense cells, dephosphorylation was prolonged by 2.6-fold with a t(1/2) of 87+/-11 sec compared to a t(1/2) of 34+/-6 sec in control cells. EGF receptor dephosphorylation was also prolonged in LAR antisense cells. These results are further evidence that LAR is a physiological regulator of the insulin receptor and is consistent with its direct interaction with the tyrosine phosphorylated insulin receptor.
Mooney
R A
RA
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
Kulas
D T
DT
Bleyle
L A
LA
Novak
J S
JS
D000818:Animals; D016373:DNA, Antisense; D066246:ErbB Receptors / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008114:Liver Neoplasms, Experimental; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000502:physiology*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; D007328:Insulin; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D066246:ErbB Receptors; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases; C516845:Ptpra protein, rat; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4