DIFFERENTIAL-EFFECTS OF ACTIVATION OF PROTEIN-KINASE-C AND CYCLIC-AMP-DEPENDENT PROTEIN-KINASE ON SODIUM-DEPENDENT PHOSPHATE-UPTAKE IN NIH-3T3 CELLS

Activation of protein kinase C (PKC) by phorbol ester (PMA), or by dia cylglycerol analogue (OAG) treatment of NIH 3T3 cells resulted in the rapid (within 2-5 min) stimulation (approx. 2-fold) of sodium-dependen t phosphate (P(i)) transport. Conversely, preincubation of these cells with forskolin and cholera toxin, or incubation with 8-bromo-cAMP, to activate cAMP-dependent protein kinase (PKA), resulted in a decrease in Na+/P(i) transport. Activation of either PKC or PKA did not change the V(max) of P(i) uptake. However, activation of PKC did result in an increase, white activation of PKA caused a decrease, in the affinity for P(i). These results indicate that there is differential regulation of Na+/P(i) uptake in NIH 3T3 cells by activators of PKC (stimulated) and PKA (inhibited) as a consequence of changes in the affinity of th e transporter for P(i).