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-like growth factor (IGF)-I on protein tyrosine phosphatase (PTPase) activity 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-100-insoluble fractions. Dose responses studies suggested that the effect of each hormone was mediated through its own receptor. PTPase activity was regulated by both acute and chronic insulin and IGF-I treatment. Maximal stimulation by both ligands occurred at 32 h and then declined. By using an antibody and a cDNA specific for PTPase1B, we found that the chronic stimulation of PTPase activity was accompanied by enhanced expression of PTPase1B mRNA and protein. Maximal induction of PTPase1B mRNA and protein by insulin and IGF-I occurred at 12 and 24 h, respectively. Based on these data, it can be suggested that ligand-stimulated PTPase activity might oppose tyrosine kinase-mediated insulin or IGF-I signal transmission and thus desensitize cells to long-term action by insulin and IGF-I. However, it is also possible that PTPase act as positive mediators of insulin and IGF-I action.
Kenner
K A
KA
Department of Medicine, University of California, San Diego, La Jolla 92093.
Hill
D E
DE
Olefsky
J M
JM
Kusari
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009132:Muscles / Q000187:drug effects / Q000201:enzymology*; D010455:Peptides / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology; D014158:Transcription, Genetic / Q000187:drug effects
D007328:Insulin; D010455:Peptides; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases