Signaling via a novel integral plasma membrane pool of a serine/threonine protein kinase PRK1 in mammalian cells.

Mammalian serine/threonine protein kinases, except for TGF-beta receptor kinase family, are intracellular proteins. PRK1/PKN is a member of the protein kinase C superfamily of serine/threonine kinases and is one of the first identified effectors for RhoA GTPase. However, the role of PRK1 in mediating signaling downstream of activated RhoA is largely unknown. Here, we present evidence that identifies a novel plasma membrane pool of PRK1. This integral membrane form of PRK1 is catalytically active. The phosphorylation of serine377 of PRK1 is required for its integration into membranes. This integration is essential for PRK1 to function as a Rho effector as only the integral plasma membrane PRK1 is able to initiate RhoA-mediated and ligand-dependent transcriptional activation of the androgen receptor in human epithelial cells and to mediate RhoA-induced neurite retraction in mouse neuronal cells. These results indicate that RhoA signals via the integral membrane pool of its effectors in its immediate vicinity at the plasma membrane, thus establishing a new paradigm in mammalian cell signaling.