Cell adhesion properties and effects on receptor-mediated insulin endocytosis are independent properties of pp120, a substrate of the insulin receptor tyrosine kinase.
pp120 undergoes phosphorylation by the tyrosine kinase of the insulin, not the insulin-like growth factor 1 (IGF-1), receptor. Moreover, pp120 stimulates receptor-mediated insulin, but not IGF-1, endocytosis, suggesting that pp120 phosphorylation underlies its effect on insulin endocytosis. pp120 phosphorylation also underlies its bile acid transport and tumor suppression functions. In addition to depending on the intracellular tail, the cell adhesion property of pp120 depends on Arg98 in the N-terminal IgV-like ectoplasmic domain. To investigate whether this domain mediates the effect of pp120 on insulin endocytosis, we mutated Arg98 to Ala and examined whether this mutation altered pp120 phosphorylation and its effect on ligand endocytosis in transfected NIH 3T3 cells. This mutation did not modify either pp120 phosphorylation or its effect on receptor-mediated ligand endocytosis. These findings support the hypothesis that stimulation of insulin endocytosis by pp120 is not mediated by Arg98 in the N-terminal IgV-like ectoplasmic domain of pp120.
Soni
P
P
Department of Pharmacology and Therapeutics, Medical College of Ohio, Toledo 43614-5804, USA.
Al-Hosaini
K A
KA
Fernström
M A
MA
Najjar
S M
SM
D016475:3T3 Cells; D019943:Amino Acid Substitution; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D004705:Endocytosis / Q000235:genetics* / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008024:Ligands; D051379:Mice; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D007328:Insulin; D008024:Ligands; D007334:Insulin-Like Growth Factor I; C410467:insulin receptor tyrosine kinase; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse