Bumetanide‐sensitive Na+ /K+ /Cl− transporter is stimulated by phorbol ester and different mitogens in quiescent human skin fibroblasts

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Abstract
In this study we investigated the correlation between the mitogenic effect and stimulation of Rb + (K + ) fluxes in human skin fibroblasts treated by purified growth factors. Both K+ transporters, bumetanide‐sensitive and ouabain‐sensitive, are stimulated 2‐3‐fold after addition of either fetal calf serum or purified recombinant growth factors to quiescent G0/G1 human skin fibroblasts. Three groups of mitogens were compared: (i) the phorbol ester 2‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA); (ii) growth factors that stimulate inositol phosphate hydrolysis and subsequently activate protein kinase C—fibroblast growth factor (FGF), platelet derived growth factor (PDGF), and α‐thrombin; and (iii) growth factors that do not activate kinase C—insulin‐like growth factor‐1 (IGF‐1), and transforming like growth‐factor‐α (TGF‐α). The three groups of mitogens stimulated human skin fibroblasts proliferation and Rb+ influxes in a similar dose‐dependent fashion. The results indicate that both the bumetanide‐sensitive and the ouabain‐sensitive Rb+ fluxes are stimulated by protein kinase C‐dependent and by the protein kinase C‐independent pathways of the mitogenic signal.

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