title: Phorbol 12-myristate 13-acetic acid inhibits PTP1B activity in human mesangial cells. A possible mechanism of enhanced tyrosine phosphorylation.
abstract: Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetic acid (PMA) stimulates DNA synthesis in human glomerular mesangial cells. Incubation of these cells with PMA stimulates the tyrosine phosphorylation of a set of proteins ranging from 110 to 39 kDa with different time kinetics. PMA inhibits total protein tyrosine phosphatase (PTPase) activity in these cells. Immunoprecipitation of PTP1B, an intracytoplasmic tyrosine phosphatase, with subsequent assay of the immunobeads for PTPase shows a significant inhibition of its activity in PMA-treated cells. Immunoblot analysis of mesangial cell lysates using the same antibody revealed that PMA does not affect the level of this 50 kDa PTP1B protein. These data indicate that inhibition of total PTPase, and specifically PTP1B, activity may provide a mechanism for stimulation of tyrosine phosphorylation by PMA in these cells and thereby contribute to its mitogenic effect.
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
authors.forename: H
authors.initials: H
authors.lastname: Kiyomoto
authors.forename: B
authors.initials: B
authors.lastname: Fouqueray
authors.forename: H E
authors.initials: HE
authors.lastname: Abboud
authors.forename: G G
authors.initials: GG
authors.lastname: Choudhury
mesh_terms: D005920:Glomerular Mesangium / Q000201:enzymology*; D006801:Humans; D007163:Immunosorbent Techniques; D007700:Kinetics; D010766:Phosphorylation; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D019000:Phosphotyrosine; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases; D013755:Tetradecanoylphorbol Acetate