REGULATION OF PROTEIN-TYROSINE PHOSPHATASES BY INSULIN AND INSULIN-LIKE GROWTH FACTOR-I

In this study, we have examined the effects of insulin and insulin-lik e growth factor (IGF)-I on protein tyrosine phosphatase (PTPase) activ ity in rat L6 skeletal muscle cells. Under basal conditions, about 85% of total cellular PTPase activity was associated with the particulate (Triton X-100-soluble) fraction. Incubation of the cells with 100 nm insulin or IGF-I significantly increased particulate PTPase activity ( p < 0.005) without altering activity in the supernatant or Triton X-10 0-insoluble fractions. Dose response studies suggested that the effect of each hormone was mediated through its own receptor. PTPase activit y was regulated by both acute and chronic insulin and IGF-I treatment. Maximal stimulation by both ligands occurred at 32 h and then decline d. By using an antibody and a cDNA specific for PTPase1B, we found tha t the chronic stimulation of PTPase activity was accompanied by enhanc ed expression of PTPase1B mRNA and protein. Maximal induction of PTPas e1B mRNA and protein by insulin and IGF-I occurred at 12 and 24 h, res pectively. Based on these data, it can be suggested that ligand-stimul ated PTPase activity might oppose tyrosine kinase-mediated insulin or IGF-I signal transmission and thus desensitize cells to long-term acti on by insulin and IGF-I. However, it is also possible that PTPases act as positive mediators of insulin and IGF-I action.