title: Interaction of constitutive photomorphogenesis 1 protein with protein-tyrosine phosphatase 1B suppresses protein-tyrosine phosphatase 1B activity and enhances insulin signaling.
abstract: Recent studies reveal that COP1 suppresses the expression of gluconeogenetic genes and prohibits hepatic glucose production. To get more insight into COP1 in hepatic cells, we examined the impact of COP1 on insulin-responsive genes and insulin signaling. We found that COP1 increased the responsiveness of insulin-modulated genes to insulin in that it promoted the expression of insulin-induced genes and inhibited that of insulin-suppressed genes and that COP1 enhanced insulin signaling as it promoted phosphorylation of Akt and ERK as well as tyrosine phosphorylation of IRβ induced by insulin. To delineate the mechanism under which COP1 modulates insulin signaling, we examined the possibility that COP1 modulates the activity of PTP1B, the major insulin receptor tyrosine phosphatase. The results indicated that COP1 physically interacted with PTP1B and suppressed PTP1B phosphatase activity as well as the association of PTP1B with IRβ. We suggest that COP1 is a positive regulator of hepatic insulin signaling.
authors: Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, USA.
authors: Wenying
authors: W
authors: Ren
authors: Yingmin
authors: Y
authors: Sun
authors: Sarwat
authors: S
authors: Cheema
authors: Keyong
authors: K
authors: Du
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D007328:Insulin; D009687:Nuclear Proteins; C471981:COP1 protein, human; C471982:COP1 protein, mouse; D044767:Ubiquitin-Protein Ligases; C435941:INSR protein, human; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse