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 (TG F)-alpha stimulated proliferation of type II cells in vitro. The mitog enic effect of TGF-alpha could be blocked by the addition of the tyros ine kinase inhibitors genistein or tyrphostin. Tyrosine phosphorylatio n in type II eels exposed to growth factors was examined using an anti phosphotyrosine 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, return ing to baseline by 30 min. As expected, genistein or tyrphostin decrea sed the TGF-alpha-induced phosphorylation of the EGF-R. Addition of TG F-beta resulted in no newly phosphorylated tyrosine proteins. TGF-beta decreased the TGF-alpha-induced phosphorylation of the EGF-R. Previou s work has shown that TGF-beta blocks the TGF-alpha stimulation of typ e II cell proliferation. It appears that TGF-beta interferes with TGF- alpha-induced phosphorylation of the EGF-R.