p21-activated protein kinase γ-PAK in pituitary secretory granules phosphorylates prolactin

p21-activated protein kinase γ-PAK phosphorylates prolactin (PRL) in rat pituitary secretory granules on Ser-177 and on the equivalent site, Ser-179, in recombinant human PRL. This is shown by comparison of phosphopeptide maps with the human PRL mutant S179D. γ-PAK is present in rat and bovine granules as identified by in-gel phosphorylation of histone H4, and by immunoblotting. Thus, phosphorylation of PRL by γ-PAK in granules produces the PRL molecule that has been shown to antagonize the growth-promoting activity of unmodified PRL, and is consistent with the identified role of γ-PAK in the induction and maintenance of cytostasis.