Estradiol activates p60src, p53/56lyn and renatured p50/55 protein tyrosine kinases in the dog prostate.
Protein tyrosine kinases (PTKs) are key enzymes implicated in signal transduction pathways regulated by growth factors (GFs). We have previously shown by immunohistochemistry that the level of phosphotyrosine (pY) proteins is increased in prostatic basal epithelial cells following estrogen treatment in castrated dogs. In this study, we investigated if this treatment increases the level and distribution of prostatic PTK activity, and more specifically, if it alters the expression and/or activity of the Src family members p60src and p53/56lyn. Prostates from normal and hyperplastic dog prostates, as well as those from castrated dogs treated with androgens, were also examined. Only the glands obtained from estrogen-treated dogs had a significantly increased total and specific PTK activity, observed uniquely in the particulate extract, as compared to the other types of prostates studied. In addition, this increased activity was correlated upon gel filtration chromatography with the presence of an additional peak of activity with an apparent molecular weight of 130 kDa, which was absent in other prostate fractions presenting only 50 kDa peaks. Using antibodies, we demonstrate that active p60src and pp53/56lyn kinases accounted for 81% of the activity in this 130 kDa peak. On the other hand, in situ renaturation also revealed the presence of still uncharacterized 50/55 kDa PTKs in the 130 kDa peak. Altogether, these findings raise the possibility that these PTKs contribute to the transmission of mitogenic signals originating directly or indirectly from estrogen stimulation of the basal cell layer of the prostate.
Allard
P
P
Department of Biochemistry, University of Montreal, Maisonneuve-Rosemont Hospital, Quebec, Canada.
Atfi
A
A
Landry
F
F
Chapdelaine
A
A
Chevalier
S
S
D000818:Animals; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D008297:Male; D008970:Molecular Weight; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D011467:Prostate / Q000201:enzymology*; D011489:Protein Denaturation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
D004958:Estradiol; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases