Hyperplasia of the thyroid gland induced by
propylthiouracil (PTU) is a well established model of rapid cell proliferation in vivo. Recent evidence indicates that
tyrosine kinase activity is associated with
growth factor receptors and
oncogene protein products and may have an important regulatory action in the control of cell growth. Thus, we examined
tyrosine kinase activity in rat thyroid membrane and cytosol preparations at rest and during PTU-induced
hyperplasia. Although
kinase activity was present in a crude microsomal membrane preparation, no change was observed during thyroid growth. In contrast,
tyrosine kinase activity assayed with the artificial substrate poly(
Glu,Na:Tyr) 4:1 was present in normal rat thyroid cytosol and increased 2- to 6-fold during the rapid phase of
hyperplasia in the first 5-10 days of PTU treatment. It declined to control values by day 15, when the size and
DNA content of the thyroid reached a plateau. Preincubation of the cytosolic preparations with several
peptides known to bind to and activate
growth factor receptor tyrosine kinases failed to enhance the activity, suggesting, along with the cytosolic localization, that the activity was distinct from these receptors. By gel filtration chromatography and
polyacrylamide gel electrophoresis,
tyrosine kinase activity was associated with a 55 kDa
protein. Partial purification over a poly(
Glu,Na:Tyr)4:1-
Sepharose column, yielded a
protein that appeared capable of autophosphorylation. It is suggested that this
tyrosine kinase plays a role in mediating the growth-promoting effects of this model of thyroid cell
hyperplasia.