Tyrosine kinase activity is necessary for growth factor-stimulated rabbit type II pneumocyte proliferation.
Tyrosine kinases are important in the signal transduction of a number of growth factors. As shown previously, transforming growth factor (TGF)-alpha stimulated proliferation of type II cells in vitro. The mitogenic effect of TGF-alpha could be blocked by the addition of the tyrosine kinase inhibitors genistein or tyrphostin. Tyrosine phosphorylation in type II cells exposed to growth factors was examined using an antiphosphotyrosine antibody. After addition of TGF-alpha, phosphorylation of a tyrosine protein with a molecular mass of 170 kD, presumed to be the epidermal growth factor receptor (EGF-R), peaked by 5 min, returning to baseline by 30 min. As expected, genistein or tyrphostin decreased the TGF-alpha-induced phosphorylation of the EGF-R. Addition of TGF-beta resulted in no newly phosphorylated tyrosine proteins. TGF-beta decreased the TGF-alpha-induced phosphorylation of the EGF-R. Previous work has shown that TGF-beta blocks the TGF-alpha stimulation of type II cell proliferation. It appears that TGF-beta interferes with TGF-alpha-induced phosphorylation of the EGF-R.
Chess
P R
PR
Department of Pediatrics, University of Rochester, Strong Children's Research Center, New York 14642.
Ryan
R M
RM
Finkelstein
J N
JN
D000230:Adenocarcinoma; D000818:Animals; D015153:Blotting, Western; D002396:Catechols / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D007700:Kinetics; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008970:Molecular Weight; D009570:Nitriles / Q000494:pharmacology; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D020032:Tyrphostins
D002396:Catechols; D007529:Isoflavones; D009570:Nitriles; D010750:Phosphoproteins; D016211:Transforming Growth Factor alpha; D020032:Tyrphostins; C060152:tyrphostin 47; D019000:Phosphotyrosine; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases