Phorbol esters induce differentiation in a pre-B-lymphocyte cell line by enhancing Na+/H+ exchange.

Published

Journal Article

The murine pre-B-lymphocyte cell line 70Z /3 may be induced to differentiate to a surface immunoglobulin-positive phenotype by the polyclonal B-cell mitogen, lipopolysaccharide. This is accomplished via activation of an amiloride-sensitive Na+-uptake system ( Rosoff , P. M., and Cantley , L. C. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 7547-7550). Here we show that the active tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) also induces surface IgM expression in 70Z /3 cells. TPA also appears to work by activating a plasma membrane Na+/H+ exchange system. A significant increase in cellular Na+ was detected within 10 min after TPA addition and by 2 h an 80% increase was observed. Amiloride blocked both the induction of surface IgM and the increase in cellular Na+. Further evidence that both TPA and lipopolysaccharide activate Na+/H+ exchange was provided by measurements of intracellular pH with carboxyfluorescein. Both TPA and lipopolysaccharide caused a 0.15 unit increase in cytoplasmic pH within 5 min after addition to the cells at 37 degrees C. The pH change required high extracellular Na+ and was inhibited by amiloride. These data suggest a mechanism by which phorbol esters affect cellular growth and differentiation.

Full Text

Duke Authors

Cited Authors

  • Rosoff, PM; Stein, LF; Cantley, LC

Published Date

  • June 1, 1984

Published In

Volume / Issue

  • 259 / 11

Start / End Page

  • 7056 - 7060

PubMed ID

  • 6144681

Pubmed Central ID

  • 6144681

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

International Standard Serial Number (ISSN)

  • 0021-9258

Language

  • eng