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(Received for publication, August 31, 1996, and in revised form, November 4, 1996)
From the Department of Biochemistry, Vanderbilt University School
of Medicine, Nashville, Tennessee 37232-0146
The intraperitoneal injection of a
vanadate/H2O2 mixture (peroxovanadate) into
mice resulted within minutes in the appearance of numerous
tyrosine-phosphorylated proteins in the liver and kidney. These effects
are presumably due to the inhibition of phosphotyrosine
phosphatase activity. Three of the tyrosine-phosphorylated proteins
have been identified as the receptors for epidermal growth factor,
insulin, and hepatocyte growth factor. The injection of peroxovanadate
also enhanced the tyrosine phosphorylation of many of the proteins
known to function downstream of these receptors, including SHC, signal
transducer and activator of transcription (Stat) 1
Volume 272, Number 2,
Issue of January 10, 1997
pp. 1263-1267
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
,
, Stat 3, Stat
5, phospholipase C-
, insulin receptor substrate 1, GTPase-activating
protein, -catenin, -catenin, p120cas, SHP-1, and SHP-2.
The administration of peroxovanadate also induced nuclear translocation
of a number of tyrosine-phosphorylated Stat proteins. In addition, the
global effects on tyrosine phosphorylation permitted the detection of a
number of novel intracellular protein interactions, including an
association of Tyk2 with -catenin. The in situ
administration of peroxovanadate may prove useful in the search for
novel tyrosine-phosphorylated proteins and the identification of new
interactions between previously identified tyrosine-phosphorylated
substrates.
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