title: Induction of hyperphosphorylation and activation of the p56lck protein tyrosine kinase by phenylarsine oxide, a phosphotyrosine phosphatase inhibitor.
abstract: The T cell protein tyrosine kinase p56lck is implicated in thymic development and mitogenic activation of T lymphocytes, and is itself regulated by reversible tyrosine phosphorylation. When phenylarsine oxide (PAO), a membrane-permeable inhibitor of phosphotyrosine phosphatases, was added to Jurkat T leukemia or LSTRA thymoma cells, the phosphate content of p56lck increased rapidly. The sites of increased phosphorylation were mapped to Tyr-192, Tyr-394 and Tyr-505. Hyperphosphorylated p56lck displayed retarded mobility on SDS gels, unaltered or marginally increased cytoskeletal association, and its catalytic activity changed in a biphasic manner; during the first 10-20 min of PAO-treatment the activity increased and then it declined to very low values within 1-2 hr. Our data suggest that p56lck contains both positive and negative regulatory sites which are constantly dephosphorylated at an unexpectedly high rate by cellular phosphotyrosine phosphatases.
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, California 92037.
authors.forename: C
authors.initials: C
authors.lastname: Oetken
authors.forename: M
authors.initials: M
authors.lastname: von Willebrand
authors.forename: A
authors.initials: A
authors.lastname: Marie-Cardine
authors.forename: T
authors.initials: T
authors.lastname: Pessa-Morikawa
authors.forename: A
authors.initials: A
authors.lastname: Ståhls
authors.forename: S
authors.initials: S
authors.lastname: Fisher
authors.forename: T
authors.initials: T
authors.lastname: Mustelin
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D002461:Cell Line, Transformed; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D010449:Peptide Mapping; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D001152:Arsenicals; D010761:Phosphorus Radioisotopes; C029341:oxophenylarsine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017027:Protein Tyrosine Phosphatases