PEROXOVANADATE INDUCES TYROSINE PHOSPHORYLATION OF MULTIPLE SIGNALINGPROTEINS IN MOUSE-LIVER AND KIDNEY

The intraperitoneal injection of a vanadate/H2O2 mixture (peroxovanada te) into mice resulted within minutes in the appearance of numerous ty rosine-phosphorylated proteins in the liver and kidney, These effects are presumably due to the inhibition of phosphotyrosine phosphatase ac tivity, Three of the tyrosine-phosphorylated proteins have been identi fied as the receptors for epidermal growth factor, insulin, and hepato cyte growth factor. The injection of peroxovanadate also enhanced the tyrosine phosphorylation of many of the proteins known to function dow nstream of these receptors, including SHC, signal transducer and activ ator of transcription (Stat) 1 alpha,beta, Stat 3, Stat 5, phospholipa se C-gamma, insulin receptor substrate 1, GTPase-activating protein, b eta-catenin, gamma-catenin, p120(cas), SHP-1, and SHP-2. The administr ation of peroxovanadate also induced nuclear translocation of a number of tyrosine-phosphorylated Stat proteins, In addition, the global eff ects on tyrosine phosphorylation permitted the detection of a number o f novel intracellular protein interactions, including an association o f Tyk2 with beta-catenin. The in situ administration of peroxovanadate may prove useful in the search for novel tyrosine-phosphorylated prot eins and the identification of new interactions between previously ide ntified tyrosine-phosphorylated substrates.