p21-Activated kinase 2 (PAK2) inhibits TGF-β signaling in Madin-Darby canine kidney (MDCK) epithelial cells by interfering with the receptor-Smad interaction.

TGF-β (transforming growth factor β) plays a variety of cellular functions mainly through the Smad pathway. Phosphorylation of the carboxyl SXS motif in R-Smads (Smad2 and Smad3) by the type I receptor TβRI is a key step for their activation. It has been reported that the serine/threonine kinase PAK2 (p21-activated kinase 2) can mediate TGF-β signaling in mesenchymal cells.

Activation of Syk protein tyrosine kinase in response to osmotic stress requires interaction with p21-activated protein kinase Pak2/gamma-PAK.

The p21-activated serine/threonine protein kinase Pak2/gamma-PAK and the nonreceptor type of protein tyrosine kinase Syk are known to be activated when the cells are exposed to osmotic stress. The purpose of the present study was to examine whether Pak2 and Syk functionally cooperate in cellular signaling. Cotransfection studies revealed that Pak2 associates with Syk in COS cells.

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

p21-activated protein kinase gamma-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. gamma-PAK is present in rat and bovine granules as identified by in-gel phosphorylation of histone H4, and by immunoblotting.