Phosphorylation-Dephosphorylation of Renal Phenylalanine Hydroxylase

The role of reversible phosphorylation in the hormonal control of phenylalanine hydroxylase in isolated rat proximal kidney tubules

“…Incubation of proximal tubules with okadaic acid, a potent protein phosphatase 1 and 2A inhibitor (Hardie et al, 1991), also brought about an increase in hydroxylase phosphorylation (see Table 1 and Figure 1). These alterations are of a similar magnitude to those which we, and others, have observed after incubation of isolated liver cells with okadaic acid (Green and Fisher, 1991;Doskeland et al, 1992) and are consistent with the suggestion that the major protein phosphatase activity responsible for the dephosphorylation of phenylalanine hydroxylase, under physiological conditions, is protein phosphatase 2A (Pelech et al, 1984). It should be noted that an alternative explanation for the impact of okadaic acid on phenylalanine hydroxylase phosphorylation state has recently been advanced (Doskeland et al, 1992).…”

“…In contrast, the possible role of reversible phosphorylation in the regulation of the renal enzyme has received little attention. Although the work of Rao and Kaufman (1986) indicated that the enzyme purified from renal tissues was a phosphoprotein, we have only recently been able to demonstrate the cyclic AMPdependent phosphorylation of the purified renal enzyme (Richardson et al, 1991).…”

“…Changes in phosphorylation state of the enzyme are closely associated with alterations in the tetrahydrobiopterin-dependent enzymic activity (Abita et al, 1976). We have recently shown that the enzyme purified from kidney is a substrate for cyclic AMP-dependent phosphorylation in vitro (Richardson et al, 1991). In addition, we have also been able to demonstrate that the phosphorylation state of the enzyme in isolated rat kidney tubules can be altered by incubation in the presence of dibutyryl cyclic AMP (Green et al, 1990).…”