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Vol. 15, Issue 12, 5456-5469, December 2004

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Dictyostelium PAKc Is Required for Proper Chemotaxis

Susan Lee ^*, Francisco Rivero , Kyung Chan Park ^*, Emerald Huang ^*, Satoru Funamoto ^* , and Richard A. Firtel ^* 

^* Section of Cell and Developmental Biology, Division of Biological Sciences and Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093-0380; Zentrum für Biochemie I der Medizinischen Fakultät, Universität zu Köln, 50931 Köln, Germany

Submitted April 20, 2004; Revised September 27, 2004; Accepted October 1, 2004
Monitoring Editor: Peter Devreotes

We have identified a new Dictyostelium p21-activated protein kinase, PAKc, that we demonstrate to be required for proper chemotaxis. PAKc contains a Rac-GTPase binding (CRIB) and autoinhibitory domain, a PAK-related kinase domain, an N-terminal phosphatidylinositol binding domain, and a C-terminal extension related to the G binding domain of Saccharomyces cerevisiae Ste20, the latter two domains being required for PAKc transient localization to the plasma membrane. In response to chemoattractant stimulation, PAKc kinase activity is rapidly and transiently activated, with activity levels peaking at 10 s. pakc null cells exhibit a loss of polarity and produce multiple lateral pseudopodia when placed in a chemoattractant gradient. PAKc preferentially binds the Dictyostelium Rac protein RacB, and point mutations in the conserved CRIB that abrogate this binding result in misregulated kinase activation and chemotaxis defects. We also demonstrate that a null mutation lacking the PAK family member myosin I heavy chain kinase (MIHCK) shows mild chemotaxis defects, including the formation of lateral pseudopodia. A null strain lacking both PAKc and the PAK family member MIHCK exhibits severe loss of cell movement, suggesting that PAKc and MIHCK may cooperate to regulate a common chemotaxis pathway.

Present address: Department of Neuropathology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan.

Corresponding author. E-mail address: rafirtel{at}ucsd.edu.

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