Mitogen stimulation of Na+-H+ exchange: Differential involvement of protein kinase C

Leslie Muldoon, G. A. Jamieson, A. C. Kao, H. C. Palfrey, M. L. Villereal

Research output: Contribution to journalArticle

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Abstract

The mitogen-induced activation of Na+-H+ exchange was investigated in two cultured human fibroblast strains (HSWP and WI-38 cells), that, based on previous studies, differed in their response to the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (L. M. Vincentini and M.L. Villereal, Proc. Natl. Acad. Sci. USA 82: 8053-8056, 1985). The role of protein kinase C in the activation of Na+-H+ exchange was investigated by comparing the effects of TPA on Na+ influx, in vitro phosphorylation, and in vivo phosphorylation in both cell types. Although both cell types have significant quantities of protein kinase C activity that can be activated by TPA in intact cells, the addition of TPA to intact cells stimulates Na+ influx in WI-38 cells but not in HSWP cells, indicating that in HSWP cells the stimulation of protein kinase C is not sufficient to activate the Na+-H+ exchanger. Cells were then depleted of protein kinase C activity by chronic treatment with high doses of TPA. Both HSWP and WI-38 cells were rendered protein kinase C deficient by this treatment as determined by in vitro and in vivo phosphorylation studies. Protein kinase C-deficient HSWP cells lose the ability for TPA to inhibit the serum-induced activation of Na+-H+ exchange, but there is no reduction in the stimulation of Na+ influx by serum, bradykinin, vasopressin, melittin, or vanadate, indicating that protein kinase C activity is not necessary for the mitogen-induced activation of Na+-H+ exchange in HSWP cells by agents known to stimulate phosphatidylinositol (G.A. Jamieson and M. Villereal. Arch. Biochem. Biophys. 252: 478-486, 1987). In contrast, depletion of protein kinase C activity in WI-38 cells significantly reduces both the TPA- and the serum-induced activation of the Na+-H+ exchange system, suggesting that protein kinase C activity is necessary for at least a portion of the mitogen-induced activation of the Na+-H+ exchangr in WI-38 cells. These results indicate that the mechanisms for regulating Na+-H+ exchange can differ dramatically between different types of fibroblasts.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume253
Issue number2
StatePublished - 1987
Externally publishedYes

Fingerprint

Mitogens
Protein Kinase C
Acetates
Tetradecanoylphorbol Acetate
Chemical activation
Ion exchange
Phosphorylation
Fibroblasts
Melitten
Sodium-Hydrogen Antiporter
Vanadates
Bradykinin
Arches
Phorbol Esters
Phosphatidylinositols
Vasopressins
Serum
Tumors

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Mitogen stimulation of Na+-H+ exchange : Differential involvement of protein kinase C. / Muldoon, Leslie; Jamieson, G. A.; Kao, A. C.; Palfrey, H. C.; Villereal, M. L.

In: American Journal of Physiology - Cell Physiology, Vol. 253, No. 2, 1987.

Research output: Contribution to journalArticle

Muldoon, Leslie ; Jamieson, G. A. ; Kao, A. C. ; Palfrey, H. C. ; Villereal, M. L. / Mitogen stimulation of Na+-H+ exchange : Differential involvement of protein kinase C. In: American Journal of Physiology - Cell Physiology. 1987 ; Vol. 253, No. 2.
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