Enhancement of cytosolic tyrosine kinase activity by propylthiouracil-induced hyperplasia in the rat thyroid.
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.
Polychronakos
C
C
Protein and Polypeptide Hormone Laboratory, Royal Victoria Hospital, Montreal, Quebec, Canada.
Piscina
R
R
Fantus
I G
IG
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D002850:Chromatography, Gel; D003600:Cytosol / Q000201:enzymology*; D006657:Histones / Q000378:metabolism; D006965:Hyperplasia; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D010748:Phosphopeptides / Q000378:metabolism; D010766:Phosphorylation; D011441:Propylthiouracil / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011986:Receptors, Somatotropin / Q000378:metabolism; D013961:Thyroid Gland / Q000201:enzymology / Q000473:pathology*
D006657:Histones; D010748:Phosphopeptides; D011986:Receptors, Somatotropin; D011441:Propylthiouracil; D011505:Protein-Tyrosine Kinases