cAMP-dependent protein kinase regulates renal epithelial cell properties.
Previous studies have implicated adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) in regulation of both growth and expression of differentiated function in the pig renal epithelial cell, LLC-PK1. To investigate this possible regulatory mechanism, we compared growth behavior, morphology, and appearance of two differentiated functions, Na-hexose symport (SYMP) and gamma-glutamyl transpeptidase (gamma-GT), in the LLC-PK1 line and two PKA-deficient mutants (FIB4 and FIB6). Compared with the wild-type cell line, the mutant lines continued to proliferate at higher population densities and exhibited altered cell morphology, poorer formation of the brush-border structure, and decreased or lack of expression of SYMP and gamma-GT activities. Wild-type and mutant cells exhibit an identical logarithmic growth rate. Both lines form cell-cell junctions and exhibit identical kinetic properties of expressed SYMP activity. These results strongly support the hypothesis that PKA modulates a defined subset of cellular processes, including aspects of growth control and expression of the differentiated phenotype, in this renal epithelial cell line.
Amsler
K
K
Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway 08854.
Ghatani
S
S
Hemmings
B A
BA
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication; D004848:Epithelium / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D006706:Homeostasis; D007668:Kidney; D007700:Kinetics; D008757:Methylglucosides / Q000378:metabolism; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010695:Phlorhizin / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D008757:Methylglucosides; C027020:methylglucoside; D010695:Phlorhizin; D005723:gamma-Glutamyltransferase; D011494:Protein Kinases; D015056:1-Methyl-3-isobutylxanthine; D013936:Thymidine