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Originally published In Press as doi:10.1074/jbc.C000806200 on January 22, 2001
J. Biol. Chem., Vol. 276, Issue 14, 10581-10584, April 6, 2001
ACCELERATED PUBLICATION
Leucine Zipper-mediated Homodimerization of the
p21-activated Kinase-interacting Factor, Pix
IMPLICATION FOR A ROLE IN CYTOSKELETAL REORGANIZATION*
Seyun
Kim,
Seung-Hye
Lee, and
Dongeun
Park
From the School of Biological Sciences, Seoul National University,
Seoul 151-742, Republic of Korea
Pix, a p21-activated kinase-interacting exchange
factor, is known to be involved in the regulation of Cdc42/Rac GTPases.
The 85-kDa Pix-a protein contains an Src homology 3 domain,
the tandem Dbl homology and Pleckstrin homology domains, a proline-rich
region, and a GIT1-binding domain. In addition to those domains,
Pix-a also contains a putative leucine zipper domain at the
C-terminal end. In this study, we demonstrate that the
previously identified putative leucine zipper domain mediates the
formation of Pix-a homodimers. Using in vitro and
in vivo methodologies, we show that deletion of the leucine
zipper domain is sufficient to abolish Pix-a homodimerization. In
NIH3T3 fibroblast cells, expression of wild type Pix-a induces the
formation of membrane ruffles. However, cells expressing the leucine
zipper domain deletion mutant could not form membrane ruffle
structures. Moreover, platelet-derived growth factor-mediated
cytoskeletal changes were completely blocked by the leucine zipper
domain deletion mutant. The results suggest that the leucine
zipper domain enables Pix-a to homodimerize, and homodimerization is
essential for Pix-a signaling functions leading to the cytoskeletal reorganization.
*
This work was supported in part by Korea Science Foundation
(KOSEF) Grant 1998G0202 through Center for Cell Signaling
Research and by KOSEF Grant 97-0401-07-01-5. S. K. and S.-H. L. were
supported by Fellowship BK21 from the Korean Ministry of Education.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: School of Biological
Sciences, Seoul National University, Kwanak-gu, Shilim-dong, Seoul
151-742, Republic of Korea. Tel.: 82-2-880-5753; Fax: 82-2-872-1993; E-mail: depark@snu.ac.kr.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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