AN ANALYSIS OF PAK4 SIGNALING

Abstract

The serine/threonine kinase PAK4 functions downstream of Cdc42, but is restricted to metazoans. It is implicated the regulation of cell-cell junction stability and in cell motility. The goal of this thesis was to investigate how PAK4 functions in cultured cells. Here it is shown that PAK4 interacts with an unstudied ~30 kDa protein (C1orf183) termed Maya. Y2H analysis suggested that Maya acts as an adaptor linking PAK4 to the actin-regulatory protein Abi2 which is a subunit of the WAVE regulatory complex (WRC). In this context PAK4 phosphorylates Ser309 of Abi2, and that this phosphorylation is required for Abi2 to promote cell migration. These findings also indicate for the first time that PAK4 acts downstream of Cdc42 to regulate cell polarity, and demonstrate its enrichment at cell-cell junctions. This has relevance for our understanding of embryonic development, neurological diseases and PAK4 as a target of anti-cancer therapeutics.