Premium
The phorbol ester, TPA, increases transepithelial epidermal growth factor flux
Author(s) -
Mullin James M.,
McGinn Mary T.
Publication year - 1987
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(87)80956-0
Subject(s) - protein kinase c , mannitol , epidermal growth factor , activator (genetics) , chemistry , flux (metallurgy) , permeability (electromagnetism) , biophysics , microbiology and biotechnology , kinase , biology , biochemistry , receptor , membrane , organic chemistry
Exposure of cultured kidney epithelial (LLC‐PK 1 ) cell sheets to 10 −7 M TPA, a potent tumor promoter and activator of protein kinase C, initiates within minutes a drop in the transepithelial voltage across these sheets. This fall in potential difference correlates with an over 40‐fold increase in the transepithelial flux of 1 mM D‐mannitol, suggesting that the intercellular junctions have become leaky. Dual labeling experiments with 1 mM D‐[ 14 C]mannitol and 10 nM 125 I‐EGF show that after promoter treatment, a 7‐fold increase in net 125 I flux accompanies the increase in mannitol flux. Gel filtration and gel electrophoresis indicate that for control cell sheets only 15% of the transited 125 I is actually EGF, whereas with TPA‐treated cell sheets, 60% of the 125 I which passed across is EGF. These percentages permitted determination of actual EGF flux values, and show that TPA treatment engenders a 35‐fold increase in transepithelial EGF flux. Diacylglycerols also increase the junctional permeability of these cells, thereby suggesting the involvement of protein kinase C.